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NM_004287.5(GOSR2):c.430G>T (p.Gly144Trp) AND Progressive myoclonic epilepsy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 20, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001068291.15

Allele description [Variation Report for NM_004287.5(GOSR2):c.430G>T (p.Gly144Trp)]

NM_004287.5(GOSR2):c.430G>T (p.Gly144Trp)

Genes:
GOSR2:golgi SNAP receptor complex member 2 [Gene - OMIM - HGNC]
LRRC37A2:leucine rich repeat containing 37 member A2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.32
Genomic location:
Preferred name:
NM_004287.5(GOSR2):c.430G>T (p.Gly144Trp)
HGVS:
  • NC_000017.11:g.46935122G>T
  • NG_031806.2:g.17003G>T
  • NM_001012511.3:c.430G>T
  • NM_001321133.2:c.430G>T
  • NM_001321134.2:c.282+2923G>T
  • NM_001330252.2:c.336+2923G>T
  • NM_001353114.2:c.427G>T
  • NM_001353115.2:c.333+2923G>T
  • NM_001353116.2:c.333+2923G>T
  • NM_001363851.2:c.376G>T
  • NM_004287.5:c.430G>TMANE SELECT
  • NM_004287.5:c.430G>T
  • NM_054022.4:c.430G>T
  • NP_001012529.1:p.Gly144Trp
  • NP_001308062.1:p.Gly144Trp
  • NP_001340043.1:p.Gly143Trp
  • NP_001350780.1:p.Gly126Trp
  • NP_004278.2:p.Gly144Trp
  • NP_473363.1:p.Gly144Trp
  • NC_000017.10:g.45012488G>T
  • NM_001321133.1:c.430G>T
  • NM_004287.3:c.430G>T
  • NM_054022.2:c.430G>T
  • NR_148349.2:n.463G>T
  • O14653:p.Gly144Trp
Protein change:
G126W; GLY144TRP
Links:
UniProtKB: O14653#VAR_065833; OMIM: 604027.0001; dbSNP: rs387906881
NCBI 1000 Genomes Browser:
rs387906881
Molecular consequence:
  • NM_001321134.2:c.282+2923G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001330252.2:c.336+2923G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353115.2:c.333+2923G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001353116.2:c.333+2923G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001012511.3:c.430G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321133.2:c.430G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353114.2:c.427G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363851.2:c.376G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004287.5:c.430G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_054022.4:c.430G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148349.2:n.463G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Progressive myoclonic epilepsy
Synonyms:
Myoclonic Epilepsies, Progressive; Familial progressive myoclonic epilepsy; Progressive myoclonus epilepsy; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0020074; MedGen: C0751778; Orphanet: 308; OMIM: PS254800

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001233394Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 20, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Functional assays for the assessment of the pathogenicity of variants of GOSR2, an ER-to-Golgi SNARE involved in progressive myoclonus epilepsies.

Völker JM, Dergai M, Abriata LA, Mingard Y, Ysselstein D, Krainc D, Dal Peraro M, Fischer von Mollard G, Fasshauer D, Koliwer J, Schwake M.

Dis Model Mech. 2017 Dec 19;10(12):1391-1398. doi: 10.1242/dmm.029132.

PubMed [citation]
PMID:
28982678
PMCID:
PMC5769602

A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia.

Corbett MA, Schwake M, Bahlo M, Dibbens LM, Lin M, Gandolfo LC, Vears DF, O'Sullivan JD, Robertson T, Bayly MA, Gardner AE, Vlaar AM, Korenke GC, Bloem BR, de Coo IF, Verhagen JM, Lehesjoki AE, Gecz J, Berkovic SF.

Am J Hum Genet. 2011 May 13;88(5):657-63. doi: 10.1016/j.ajhg.2011.04.011. Epub 2011 May 5.

PubMed [citation]
PMID:
21549339
PMCID:
PMC3146720
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001233394.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 144 of the GOSR2 protein (p.Gly144Trp). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GOSR2 function (PMID: 21549339, 28982678). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 30406). This missense change has been observed in individuals with progressive myoclonic epilepsy (PMID: 21549339, 23449775). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs387906881, gnomAD 0.01%).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024