Full data view for gene RARS2

Information The variants shown are described using the NM_020320.3 transcript reference sequence.

117 entries on 2 pages. Showing entries 1 - 100.
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Effect     

Exon     

AscendingDNA change (cDNA)     

RNA change     

Protein     

Allele     

Classification method     

Clinical classification     

DNA change (genomic) (hg19)     

DNA change (hg38)     

Published as     

ISCN     

DB-ID     

Variant remarks     

Reference     

ClinVar ID     

dbSNP ID     

Origin     

Segregation     

Frequency     

Re-site     

VIP     

Methylation     

Template     

Technique     

Tissue     

Remarks     

Disease     

ID_report     

Reference     

Remarks     

Gender     

Consanguinity     

Country     

Population     

Age at death     

VIP     

Data_av     

Treatment     

Panel size     

Owner     
-?/. - c.-4456C>A r.(?) p.(=) Unknown - likely benign g.88304131G>T - ORC3(NM_012381.4):c.79+6G>T - ORC3_000017 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.1A>G r.(?) p.(Met1?) Unknown - pathogenic g.88299675T>C g.87589957T>C RARS2(NM_020320.5):c.1A>G (p.M1?) - RARS2_000023 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.1A>G r.(?) p.0? Parent #2 ACMG pathogenic (recessive) g.88299675T>C g.87589957T>C - - RARS2_000023 - PubMed: Helbig 2016 - - Germline - - - - - DNA SEQ-NG - WES seizures Pat88 PubMed: Helbig 2016 - - - United States - - - - - 1 Johan den Dunnen
+?/. - c.1A>G r.(?) p.0? Unknown - likely pathogenic (recessive) g.88299675T>C - - - RARS2_000023 - - - - Germline - - - - - DNA SEQ-NG - - PCH6 - - - M no Italy - - - - - 1 Enza Maria Valente
+/. - c.1A>G r.? p.? Parent #2 - pathogenic g.88299675T>C g.87589957T>C NM_001350505.1:c.1A>G (M1V) - RARS2_000023 - PubMed: Chuan 2022 - - Germline - - - - - DNA SEQ, SEQ-NG - WES epilepsy Pat11 PubMed: Chuan 2022 - M - China - - - - - 1 Johan den Dunnen
+/. - c.1A>G r.(?) p.(Met1?) Parent #1 - pathogenic g.88299675T>C g.87589957T>C M1V - RARS2_000023 - PubMed: Legati 2016 - - Germline - - - - - DNA SEQ, SEQ-NG - - mitochondrial NGSP90 PubMed: Legati 2016 - M - - - - - - - 1 Daniele Ghezzi
+?/. - c.3G>A r.(?) p.(Met1?) Unknown - likely pathogenic g.88299673C>T - RARS2(NM_020320.4):c.3G>A (p.M1?) - ORC3_000013 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.3G>A r.? p.(Met1?) Maternal (confirmed) ACMG VUS g.88299673C>T - - - ORC3_000013 ACMG PM2, PP3; The patient's electroclinical phenotype shares some features with previous reports for this gene, namely prominent myoclonus, though later onset (not infantile) and a lack of other associated features is noted. The two ultra-rare predicted damaging variants were confirmed in trans and the parents are not related, consistent with the bi-allelic autosomal recessive inheritance. It is therefore with moderate confidence that we expand the RARS2 phenotype to PME. PubMed: Courage 2021, Journal: Courage 2021 - - Germline - - - - - DNA SEQ, SEQ-NG WES trio - PCH6 PME14 PubMed: Courage 2021, Journal: Courage 2021 - F no Italy - - - - - 1 Carolina Courage
?/. - c.7T>C r.(?) p.(Cys3Arg) Unknown - VUS g.88299669A>G g.87589951A>G RARS2(NM_020320.4):c.7T>C (p.C3R), RARS2(NM_020320.5):c.7T>C (p.C3R) - ORC3_000010 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.7T>C r.(?) p.(Cys3Arg) Unknown - VUS g.88299669A>G - RARS2(NM_020320.4):c.7T>C (p.C3R), RARS2(NM_020320.5):c.7T>C (p.C3R) - ORC3_000010 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.25A>G r.(?) p.(Ile9Val) Unknown - VUS g.88299651T>C g.87589933T>C RARS2(NM_020320.4):c.25A>G (p.I9V) - RARS2_000022 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.25A>G r.(?) p.(Ile9Val) Parent #1 - pathogenic g.88299651T>C g.87589933T>C NM_001350505.1:c.25A>G - RARS2_000022 - PubMed: Chuan 2022 - - Germline - - - - - DNA SEQ, SEQ-NG - WES epilepsy Pat2 PubMed: Chuan 2022 - M - China - - - - - 1 Johan den Dunnen
+?/. - c.28G>A r.(?) p.(Ala10Thr) Both (homozygous) ACMG likely pathogenic g.88299648C>T g.87589930C>T NM_001350505.1:c.28G>A - RARS2_000067 ACMG PM1,PM2,PP3,PP4 PubMed: Chuan 2022 - - Germline - - - - - DNA SEQ, SEQ-NG - WES epilepsy Pat130 PubMed: Chuan 2022 - F - China - - - - - 1 Johan den Dunnen
+/? 1 c.35A>G r.spl? p.(Gln12Arg) Paternal (confirmed) - pathogenic g.88299641T>C g.87589923T>C - - RARS2_000003 change affects splicing but consequences not fully characterised - - - Germline yes - - - - DNA, RNA SEQ Blood, Fibroblasts - PCH6 - - - - no - - - - - - 1 Carl Fratter
?/. - c.35A>G r.(?) p.(Gln12Arg) Unknown - VUS g.88299641T>C - RARS2(NM_020320.4):c.35A>G (p.Q12R) - RARS2_000003 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.35A>G r.(?) p.(Gln12Arg) Parent #1 - likely pathogenic (recessive) g.88299641T>C g.87589923T>C - - RARS2_000003 - PubMed: Hiatt 2023, Journal: Hiatt 2023 - - Germline - - - - - DNA SEQ, SEQ-NG - - NDD Pat24 PubMed: Hiatt 2023, Journal: Hiatt 2023 2-generation family, 2 affected, boy and affected carrier mother M - - - - - - - 2 Johan den Dunnen
-?/. - c.78A>C r.(?) p.(Thr26=) Unknown - likely benign g.88279267T>G g.87569549T>G RARS2(NM_020320.4):c.78A>C (p.T26=) - RARS2_000021 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.111-303C>A r.(=) p.(=) Unknown - benign g.88274253G>T g.87564535G>T RARS2(NM_020320.5):c.111-303C>A - RARS2_000042 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.111-21C>T r.(=) p.(=) Unknown - benign g.88273971G>A g.87564253G>A RARS2(NM_020320.5):c.111-21C>T - RARS2_000041 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.111-19T>G r.(=) p.(=) Unknown - benign g.88273969A>C g.87564251A>C RARS2(NM_020320.5):c.111-19T>G - RARS2_000040 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.155A>T r.(?) p.(Lys52Ile) Unknown - benign g.88273906T>A - RARS2(NM_020320.5):c.155A>T (p.(Lys52Ile)) - RARS2_000073 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.206C>A r.(?) p.(Ala69Glu) Unknown - VUS g.88273855G>T - RARS2(NM_020320.5):c.206C>A (p.(Ala69Glu)) - RARS2_000071 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.213+5G>A r.spl? p.? Unknown - likely benign g.88273843C>T g.87564125C>T RARS2(NM_020320.3):c.213+5G>A (p.?) - RARS2_000039 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.297+2T>G r.spl? p.? Unknown - likely pathogenic g.88272418A>C - - - RARS2_000064 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.396-5dup r.spl? p.? Unknown - likely benign g.88258376dup - RARS2(NM_001350508.1):c.-130-5dupT - RARS2_000056 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.396-5dup r.spl? p.? Unknown - benign g.88258376dup - RARS2(NM_001350508.1):c.-130-5dupT, RARS2(NM_020320.5):c.396-5dupT - RARS2_000056 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.403A>G r.(?) p.(Asn135Asp) Unknown - VUS g.88258357T>C - - - RARS2_000061 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.403A>G r.(?) p.(Asn135Asp) Unknown ACMG likely pathogenic g.88258357T>C - - - RARS2_000061 - - - rs755448382 Unknown - - - - - DNA SEQ-NG - - SIDS SIDS083 - - M - Switzerland Europe 00y04m - - - 1 Cordula Haas
+?/. - c.419T>G r.(?) p.(Phe140Cys) Parent #1 - likely pathogenic g.88258341A>C g.87548623A>C - - RARS2_000050 1 heterozygous, no homozygous; Clinindb (India) PubMed: Narang 2020, Journal: Narang 2020 - rs772887102 Germline - 1/2763 individuals - - - DNA arraySNP - Infinium Global Screening Array v1.0 ? - PubMed: Narang 2020, Journal: Narang 2020 analysis 2794 individuals (India) - - India - - - - - 1 Mohammed Faruq
+/. - c.419T>G r.(?) p.(Phe140Cys) Parent #1 ACMG pathogenic (recessive) g.88258341A>C g.87548623A>C - - RARS2_000050 - PubMed: Helbig 2016 - - Germline - - - - - DNA SEQ-NG - WES seizures Pat88 PubMed: Helbig 2016 - - - United States - - - - - 1 Johan den Dunnen
+?/. - c.419T>G r.(?) p.(Phe140Cys) Unknown - likely pathogenic g.88258341A>C g.87548623A>C - - RARS2_000050 variants reported seperately, unknown if mono-allelic or bi-allelic PubMed: Retterer 2016 - - Unknown - - - - - DNA SEQ, SEQ-NG - WES ? - PubMed: Retterer 2016 analysis proband (1/3040); possible combination of variants not reported - - United States - - - - - 1 Johan den Dunnen
+?/. - c.422A>G r.(?) p.(His141Arg) Unknown ACMG likely pathogenic g.88258338T>C - - - RARS2_000063 - - - rs377591456 Unknown - - - - - DNA SEQ-NG - - SIDS SIDS226 - - F - Switzerland Europe 00y02m - - - 1 Cordula Haas
-?/. - c.425T>C r.(?) p.(Val142Ala) Unknown - likely benign g.88258335A>G g.87548617A>G RARS2(NM_020320.4):c.425T>C (p.V142A) - RARS2_000020 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.425T>C r.(?) p.(Val142Ala) Maternal (confirmed) ACMG likely pathogenic g.88258335A>G - - - RARS2_000020 ACMG PM1, PM2, PM3; The patients' electroclinical phenotype shares some features (ataxia, myoclonus and cognitive impairment) with previous case reports for this gene, although onset is later (childhood, not infantile), and other associated features (extrapyramidal features, oculomotor apraxia) are not noted. The two ultra-rare predicted damaging variants were confirmed in trans and the parents are not related, consistent with the bi-allelic autosomal recessive inheritance. It is therefore with moderate confidence that we expand the RARS2 phenotype to PME. PubMed: Courage 2021, Journal: Courage 2021 - - Germline - - - - - DNA SEQ, SEQ-NG WES quartet - PCH6 PME12 PubMed: Courage 2021, Journal: Courage 2021 family, 2 affected (F, M) F no Italy - - - - - 2 Carolina Courage
+?/. - c.425T>C r.(?) p.(Val142Ala) Maternal (confirmed) ACMG likely pathogenic g.88258335A>G - - - RARS2_000020 ACMG PM1, PM2, PM3; The patients' electroclinical phenotype shares some features (ataxia, myoclonus and cognitive impairment) with previous case reports for this gene, although onset is later (childhood, not infantile), and other associated features (extrapyramidal features, oculomotor apraxia) are not noted. The two ultra-rare predicted damaging variants were confirmed in trans and the parents are not related, consistent with the bi-allelic autosomal recessive inheritance. It is therefore with moderate confidence that we expand the RARS2 phenotype to PME. PubMed: Courage 2021, Journal: Courage 2021 - - Germline - - - - - DNA SEQ, SEQ-NG WES quartet - PCH6 PME13 PubMed: Courage 2021, Journal: Courage 2021 relative of PME12 M no Italy - - - - - 1 Carolina Courage
+?/. - c.442A>G r.(?) p.(Thr148Ala) Parent #1 - likely pathogenic g.88258318T>C g.87548600T>C - - RARS2_000005 Functional validation will be performed PubMed: Neveling 2013 - - Unknown ? - - - - DNA SEQ - - ? - PubMed: Neveling 2013 - - - - - - - - - 1 Marcel Nelen
?/. - c.442A>G r.(?) p.(Thr148Ala) Unknown - VUS g.88258318T>C g.87548600T>C RARS2(NM_020320.4):c.442A>G (p.T148A), RARS2(NM_020320.5):c.442A>G (p.(Thr148Ala), p.T148A) - RARS2_000005 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.442A>G r.(?) p.(Thr148Ala) Unknown - VUS g.88258318T>C g.87548600T>C RARS2(NM_020320.4):c.442A>G (p.T148A), RARS2(NM_020320.5):c.442A>G (p.(Thr148Ala), p.T148A) - RARS2_000005 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.442A>G r.(?) p.(Thr148Ala) Unknown - VUS g.88258318T>C - RARS2(NM_020320.4):c.442A>G (p.T148A), RARS2(NM_020320.5):c.442A>G (p.(Thr148Ala), p.T148A) - RARS2_000005 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.442A>G r.(?) p.(Thr148Ala) Unknown - VUS g.88258318T>C - RARS2(NM_020320.4):c.442A>G (p.T148A), RARS2(NM_020320.5):c.442A>G (p.(Thr148Ala), p.T148A) - RARS2_000005 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.452-21A>G r.(=) p.(=) Unknown - benign g.88255438T>C g.87545720T>C RARS2(NM_020320.5):c.452-21A>G - RARS2_000037 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.452_453insC r.(?) p.(Asn152Lysfs*40) Unknown - VUS g.88255416_88255417insG - RARS2(NM_020320.5):c.452_453insC (p.(Asn152LysfsTer40)) - RARS2_000069 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.456T>C r.(?) p.(Asn152=) Unknown - likely benign g.88255413A>G g.87545695A>G RARS2(NM_020320.4):c.456T>C (p.N152=) - RARS2_000019 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/? 7 c.472_474del r.472_474del p.Lys158del Paternal (confirmed) - pathogenic g.88255395_88255397del g.87545677_87545679del - - RARS2_000002 - - - - Germline yes - - - - DNA, RNA SEQ Blood, Fibroblasts - PCH6 - - - - no - - - - - - 1 Carl Fratter
./. - c.472_474del r.(?) p.(Lys158del) Maternal (confirmed) - pathogenic g.88255395_88255397del g.87545677_87545679del - - RARS2_000006 in-frame deletion PubMed: DDDS 2015, Journal: DDDS 2015 - - Germline - - - - - DNA SEQ, SEQ-NG-I - - ? - PubMed: DDDS 2015, Journal: DDDS 2015 family, 1 affected M - United Kingdom (Great Britain) - - - Decipher - 1 Johan den Dunnen
+/. - c.472_474del r.(?) p.(Lys158del) Unknown - pathogenic g.88255395_88255397del g.87545677_87545679del 472_474delAAA - RARS2_000002 variants reported seperately, unknown if mono-allelic or bi-allelic PubMed: Retterer 2016 - - Unknown - - - - - DNA SEQ, SEQ-NG - WES ? - PubMed: Retterer 2016 analysis proband (1/3040); possible combination of variants not reported - - United States - - - - - 1 Johan den Dunnen
-?/. - c.528G>A r.(?) p.(Met176Ile) Unknown - likely benign g.88255341C>T g.87545623C>T RARS2(NM_020320.5):c.528G>A (p.M176I) - RARS2_000036 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.566G>A r.(?) p.(Gly189Asp) Parent #1 ACMG likely pathogenic g.88251682C>T g.87541964C>T NM_001350505.1:c.566G>A - RARS2_000066 ACMG PM1,PM2,PM3,PP3 PubMed: Chuan 2022 - - Germline - - - - - DNA SEQ, SEQ-NG - WES epilepsy Pat11 PubMed: Chuan 2022 - M - China - - - - - 1 Johan den Dunnen
+/. - c.622C>T r.(?) p.(Gln208*) Paternal (confirmed) - pathogenic g.88240651G>A g.87530933G>A - - RARS2_000049 - PubMed: Pronicka 2016 - - Germline - 1/113 cases - - - DNA SEQ, SEQ-NG - WES ? Pat41 PubMed: Pronicka 2016 2-generation family, 2 affected brothers F - Poland - - - - - 1 Johan den Dunnen
-?/. - c.635A>C r.(?) p.(Glu212Ala) Unknown - likely benign g.88240638T>G g.87530920T>G RARS2(NM_001350508.1):c.110A>C (p.E37A) - RARS2_000048 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.660A>C r.(?) p.(Ala220=) Unknown - likely benign g.88240613T>G g.87530895T>G RARS2(NM_020320.4):c.660A>C (p.A220=) - RARS2_000018 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.703G>A r.(?) p.(Val235Met) Unknown - likely benign g.88240570C>T g.87530852C>T RARS2(NM_020320.5):c.703G>A (p.V235M, p.(Val235Met)) - RARS2_000035 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.703G>A r.(?) p.(Val235Met) Parent #1 - likely benign g.88240570C>T g.87530852C>T - - RARS2_000035 233 heterozygous; Clinindb (India) PubMed: Narang 2020, Journal: Narang 2020 - rs35862137 Germline - 233/2795 individuals - - - DNA arraySNP - Infinium Global Screening Array v1.0 ? - PubMed: Narang 2020, Journal: Narang 2020 analysis 2794 individuals (India) - - India - - - - - 233 Mohammed Faruq
-?/. - c.703G>A r.(?) p.(Val235Met) Both (homozygous) - likely benign g.88240570C>T g.87530852C>T - - RARS2_000035 4 homozygous; Clinindb (India) PubMed: Narang 2020, Journal: Narang 2020 - rs35862137 Germline - 4/2795 individuals - - - DNA arraySNP - Infinium Global Screening Array v1.0 ? - PubMed: Narang 2020, Journal: Narang 2020 analysis 2794 individuals (India) - - India - - - - - 4 Mohammed Faruq
-/. - c.703G>A r.(?) p.(Val235Met) Unknown - benign g.88240570C>T - RARS2(NM_020320.5):c.703G>A (p.V235M, p.(Val235Met)) - RARS2_000035 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.726A>G r.(?) p.(Gln242=) Unknown - likely benign g.88240547T>C - RARS2(NM_001350508.1):c.201A>G (p.Q67=), RARS2(NM_020320.5):c.726A>G (p.(Gln242=)) - RARS2_000059 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.726A>G r.(?) p.(Gln242=) Unknown - likely benign g.88240547T>C - RARS2(NM_001350508.1):c.201A>G (p.Q67=), RARS2(NM_020320.5):c.726A>G (p.(Gln242=)) - RARS2_000059 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.754T>A r.(?) p.(Tyr252Asn) Unknown - VUS g.88240519A>T g.87530801A>T RARS2(NM_001350508.1):c.229T>A (p.Y77N), RARS2(NM_020320.5):c.754T>A (p.(Tyr252Asn)) - RARS2_000047 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.754T>A r.(?) p.(Tyr252Asn) Unknown - VUS g.88240519A>T g.87530801A>T RARS2(NM_001350508.1):c.229T>A (p.Y77N), RARS2(NM_020320.5):c.754T>A (p.(Tyr252Asn)) - RARS2_000047 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.754T>A r.(?) p.(Tyr252Asn) Unknown - VUS g.88240519A>T - RARS2(NM_001350508.1):c.229T>A (p.Y77N), RARS2(NM_020320.5):c.754T>A (p.(Tyr252Asn)) - RARS2_000047 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.770A>G r.(?) p.(Lys257Arg) Unknown - VUS g.88240503T>C - RARS2(NM_020320.5):c.770A>G (p.K257R) - RARS2_000072 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.773G>A r.(?) p.(Arg258His) Unknown - pathogenic g.88239365C>T g.87529647C>T RARS2(NM_020320.5):c.773G>A (p.(Arg258His), p.R258H) - RARS2_000027 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.773G>A r.(?) p.(Arg258His) Unknown - likely pathogenic g.88239365C>T - RARS2(NM_020320.5):c.773G>A (p.(Arg258His), p.R258H) - RARS2_000027 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.773G>A r.(?) p.(Arg258His) Unknown - VUS g.88239365C>T - RARS2(NM_020320.5):c.773G>A (p.(Arg258His), p.R258H) - RARS2_000027 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. 10 c.795del r.(?) p.(Glu265Aspfs*16) Maternal (confirmed) - pathogenic (recessive) g.88239344del g.87529626del 795delA - RARS2_000029 - - - - Germline - - - - - DNA PCR, SEQ-NG - - PCH6 - - - - - - - - - - - 1 Carolina Courage
?/. - c.818G>C r.(?) p.(Arg273Pro) Unknown - VUS g.88239320C>G - RARS2(NM_001350508.1):c.293G>C (p.R98P) - RARS2_000058 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
./. - c.848T>A r.(?) p.(Leu283Gln) Paternal (confirmed) - pathogenic g.88239290A>T g.87529572A>T - - RARS2_000007 - PubMed: DDDS 2015, Journal: DDDS 2015 - - Germline - - - - - DNA SEQ, SEQ-NG-I - - ? - PubMed: DDDS 2015, Journal: DDDS 2015 family, 1 affected M - United Kingdom (Great Britain) - - - Decipher - 1 Johan den Dunnen
-/. - c.872A>G r.(?) p.(Lys291Arg) Unknown - benign g.88239266T>C g.87529548T>C RARS2(NM_020320.5):c.872A>G (p.K291R) - RARS2_000017 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.888G>C r.(?) p.(Thr296=) Unknown - likely benign g.88234361C>G - RARS2(NM_001350508.1):c.363G>C (p.T121=), RARS2(NM_020320.5):c.888G>C (p.(Thr296=)) - RARS2_000051 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.888G>C r.(?) p.(Thr296=) Unknown - benign g.88234361C>G - RARS2(NM_001350508.1):c.363G>C (p.T121=), RARS2(NM_020320.5):c.888G>C (p.(Thr296=)) - RARS2_000051 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.943C>T r.(?) p.(Arg315*) Paternal (confirmed) ACMG pathogenic g.88234306G>A - - - RARS2_000052 ACMG PVS1, PM2, PP3, PP5; The patients' electroclinical phenotype shares some features (ataxia, myoclonus and cognitive impairment) with previous case reports for this gene, although onset is later (childhood, not infantile), and other associated features (extrapyramidal features, oculomotor apraxia) are not noted. The two ultra-rare predicted damaging variants were confirmed in trans and the parents are not related, consistent with the bi-allelic autosomal recessive inheritance. It is therefore with moderate confidence that we expand the RARS2 phenotype to PME. PubMed: Courage 2021, Journal: Courage 2021 - - Germline - - - - - DNA SEQ, SEQ-NG WES quartet - PCH6 PME12 PubMed: Courage 2021, Journal: Courage 2021 family, 2 affected (F, M) F no Italy - - - - - 2 Carolina Courage
+/. - c.943C>T r.(?) p.(Arg315*) Paternal (confirmed) ACMG pathogenic g.88234306G>A - - - RARS2_000052 ACMG PVS1, PM2, PP3, PP5; The patients' electroclinical phenotype shares some features (ataxia, myoclonus and cognitive impairment) with previous case reports for this gene, although onset is later (childhood, not infantile), and other associated features (extrapyramidal features, oculomotor apraxia) are not noted. The two ultra-rare predicted damaging variants were confirmed in trans and the parents are not related, consistent with the bi-allelic autosomal recessive inheritance. It is therefore with moderate confidence that we expand the RARS2 phenotype to PME. PubMed: Courage 2021, Journal: Courage 2021 - - Germline - - - - - DNA SEQ, SEQ-NG WES quartet - PCH6 PME13 PubMed: Courage 2021, Journal: Courage 2021 relative of PME12 M no Italy - - - - - 1 Carolina Courage
?/. - c.948T>A r.(?) p.(Ser316Arg) Unknown - VUS g.88234301A>T - RARS2(NM_001350508.1):c.423T>A (p.S141R) - RARS2_000055 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. 11 c.961C>T r.(?) p.(Leu321Phe) Paternal (confirmed) - likely pathogenic g.88234288G>A g.87524570G>A - - RARS2_000028 - - - - Germline - - - - - DNA PCR, SEQ-NG - - PCH6 - - - - - - - - - - - 1 Carolina Courage
?/. - c.961C>T r.(?) p.(Leu321Phe) Unknown - VUS g.88234288G>A - RARS2(NM_020320.5):c.961C>T (p.(Leu321Phe)) - RARS2_000028 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.961C>T r.(?) p.(Leu321Phe) Unknown - likely pathogenic g.88234288G>A - RARS2(NM_020320.5):c.961C>T (p.(Leu321Phe)) - RARS2_000028 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.991A>G r.(?) p.(Ile331Val) Unknown - likely benign g.88231226T>C g.87521508T>C RARS2(NM_020320.5):c.991A>G (p.(Ile331Val), p.I331V) - RARS2_000033 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.991A>G r.(?) p.(Ile331Val) Unknown - likely benign g.88231226T>C - RARS2(NM_020320.5):c.991A>G (p.(Ile331Val), p.I331V) - RARS2_000033 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/? 12 c.1024A>G r.1024a>g p.Met342Val Maternal (confirmed) - pathogenic g.88231193T>C g.87521475T>C - - RARS2_000004 - - - - Germline yes - - - - DNA, RNA SEQ Blood, Fibroblasts - PCH6 - - - - no - - - - - - 1 Carl Fratter
?/. - c.1026G>A r.(?) p.(Met342Ile) Unknown - VUS g.88231191C>T g.87521473C>T RARS2(NM_001350508.1):c.501G>A (p.M167I) - RARS2_000026 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.1026G>A r.(?) p.(Met342Ile) Maternal (confirmed) - likely pathogenic (recessive) g.88231191C>T g.87521473C>T - - RARS2_000026 - PubMed: Minardi 2020 - - Germline - - - - - DNA SEQ-NG-I - - EE - PubMed: Minardi 2020 - - - - - - - - - 1 Francesca Bisulli
+?/. - c.1026G>A r.(?) p.(Met342Ile) Maternal (confirmed) - likely pathogenic (recessive) g.88231191C>T g.87521473C>T - - RARS2_000026 - PubMed: Pronicka 2016 - - Germline - 1/113 cases - - - DNA SEQ, SEQ-NG - WES ? Pat41 PubMed: Pronicka 2016 2-generation family, 2 affected brothers F - Poland - - - - - 1 Johan den Dunnen
?/. - c.1026G>A r.(?) p.(Met342Ile) Unknown - VUS g.88231191C>T - RARS2(NM_001350508.1):c.501G>A (p.M167I) - RARS2_000026 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.1026G>A r.(?) p.(Met342Ile) Paternal (confirmed) ACMG VUS g.88231191C>T - - - RARS2_000026 ACMG PM1, PM2, PP3; The patient's electroclinical phenotype shares some features with previous reports for this gene, namely prominent myoclonus, though later onset (not infantile) and a lack of other associated features is noted. The two ultra-rare predicted damaging variants were confirmed in trans and the parents are not related, consistent with the bi-allelic autosomal recessive inheritance. It is therefore with moderate confidence that we expand the RARS2 phenotype to PME. PubMed: Courage 2021, Journal: Courage 2021 - - Germline - - - - - DNA SEQ, SEQ-NG WES trio - PCH6 PME14 PubMed: Courage 2021, Journal: Courage 2021 - F no Italy - - - - - 1 Carolina Courage
-?/. - c.1123G>A r.(?) p.(Val375Met) Unknown - likely benign g.88229415C>T g.87519697C>T RARS2(NM_020320.3):c.1123G>A (p.(Val375Met)) - RARS2_000015 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.1180G>A r.(?) p.(Glu394Lys) Unknown - VUS g.88229358C>T g.87519640C>T - - RARS2_000024 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/? 14 c.1211T>A r.1211u>a p.Met404Lys Maternal (confirmed) - pathogenic g.88229327A>T g.87519609A>T - - RARS2_000001 - - - - Germline yes - - - - DNA, RNA SEQ Blood, Fibroblasts - PCH6 - - - - no - - - - - - 1 Carl Fratter
?/. - c.1236G>C r.(?) p.(Lys412Asn) Unknown - VUS g.88229302C>G - RARS2(NM_001350508.1):c.711G>C (p.K237N), RARS2(NM_020320.3):c.1236G>C (p.(Lys412Asn)) - RARS2_000054 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1236G>C r.(?) p.(Lys412Asn) Unknown - likely benign g.88229302C>G - RARS2(NM_001350508.1):c.711G>C (p.K237N), RARS2(NM_020320.3):c.1236G>C (p.(Lys412Asn)) - RARS2_000054 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+?/. - c.1305+1G>A r.spl p.? Paternal (confirmed) - pathogenic (recessive) g.88228541C>T g.87518823C>T - - RARS2_000043 - PubMed: Minardi 2020 - - Germline - - - - - DNA SEQ-NG-I - - EE - PubMed: Minardi 2020 - - - - - - - - - 1 Francesca Bisulli
-/. - c.1305+18C>T r.(=) p.(=) Unknown - benign g.88228524G>A g.87518806G>A RARS2(NM_020320.5):c.1305+18C>T - RARS2_000032 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
+/. - c.1327T>C r.(?) p.(Ser443Pro) Both (homozygous) - pathogenic g.88228436A>G g.87518718A>G NM_020320: c.T1327C; p.S443P - RARS2_000008 - PubMed: Karaca 2015 - - Germline - - - - - DNA SEQ-NG-I - WES ? 26539891-FamBAB5804 PubMed: Karaca 2015 - - - - - - - family structure in paper - 2 Johan den Dunnen
+?/. - c.1327T>C r.(?) p.(Ser443Pro) Unknown ACMG likely pathogenic g.88228436A>G - - - RARS2_000008 - - - - Germline - - - - - DNA SEQ-NG - - PCH6 - - - M no Italy - - - - - 1 Enza Maria Valente
+?/. - c.1327T>C r.(?) p.(Ser443Pro) Unknown - VUS g.88228436A>G - - - RARS2_000008 - PubMed: Razaq 2021 - - Germline/De novo (untested) - - - - - DNA SEQ, SEQ-NG - WES BMD/DMD, WEST patient PubMed: Razaq 2021 - M no United States Middle East;Hispanic - - - - 1 Johan den Dunnen
+/. - c.1327T>C r.(?) p.(Ser443Pro) Parent #2 - pathogenic g.88228436A>G g.87518718A>G S443P - RARS2_000008 - PubMed: Legati 2016 - - Germline - - - - - DNA SEQ, SEQ-NG - - mitochondrial NGSP90 PubMed: Legati 2016 - M - - - - - - - 1 Daniele Ghezzi
+?/. - c.1379G>T r.(?) p.(Gly460Val) Parent #2 ACMG likely pathogenic g.88228384C>A g.87518666C>A NM_001350505.1:c.1379G>T - RARS2_000065 ACMG PM1,PM2,PP3,PP4 PubMed: Chuan 2022 - - Germline - - - - - DNA SEQ, SEQ-NG - WES epilepsy Pat2 PubMed: Chuan 2022 - M - China - - - - - 1 Johan den Dunnen
-?/. - c.1410C>A r.(?) p.(Leu470=) Unknown - likely benign g.88228353G>T g.87518635G>T RARS2(NM_020320.4):c.1410C>A (p.L470=), RARS2(NM_020320.5):c.1410C>A (p.(Leu470=)) - RARS2_000012 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-/. - c.1410C>A r.(?) p.(Leu470=) Unknown - benign g.88228353G>T - RARS2(NM_020320.4):c.1410C>A (p.L470=), RARS2(NM_020320.5):c.1410C>A (p.(Leu470=)) - RARS2_000012 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
-?/. - c.1416-8_1416-7del r.(=) p.(=) Unknown - likely benign g.88227991_88227992del - RARS2(NM_020320.5):c.1416-8_1416-7del - RARS2_000068 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
?/. - c.1430_1431del r.(?) p.(Phe477Trpfs*7) Unknown - VUS g.88227969_88227970del - RARS2(NM_001350508.1):c.905_906delTT (p.F302Wfs*7) - RARS2_000057 VKGL data sharing initiative Nederland - - - CLASSIFICATION record - - - - - - - - - - - - - - - - - - - - - - -
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