NM_198904.4(GABRG2):c.501C>A (p.Asn167Lys) AND multiple conditions

Clinical significance:Likely pathogenic (Last evaluated: Dec 10, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000806748.1

Allele description [Variation Report for NM_198904.4(GABRG2):c.501C>A (p.Asn167Lys)]

NM_198904.4(GABRG2):c.501C>A (p.Asn167Lys)

Gene:
GABRG2:gamma-aminobutyric acid type A receptor subunit gamma2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q34
Genomic location:
Preferred name:
NM_198904.4(GABRG2):c.501C>A (p.Asn167Lys)
HGVS:
  • NC_000005.10:g.162097811C>A
  • NG_009290.1:g.35170C>A
  • NM_000816.3:c.501C>A
  • NM_000816.3:c.501C>A
  • NM_001375339.1:c.492C>A
  • NM_001375340.1:c.501C>A
  • NM_001375341.1:c.501C>A
  • NM_001375342.1:c.501C>A
  • NM_001375343.1:c.501C>A
  • NM_001375344.1:c.501C>A
  • NM_001375345.1:c.435C>A
  • NM_001375346.1:c.435C>A
  • NM_001375347.1:c.414C>A
  • NM_001375348.1:c.81C>A
  • NM_001375349.1:c.216C>A
  • NM_001375350.1:c.81C>A
  • NM_198903.2:c.501C>A
  • NM_198904.4:c.501C>AMANE SELECT
  • NP_000807.2:p.Asn167Lys
  • NP_000807.2:p.Asn167Lys
  • NP_001362268.1:p.Asn164Lys
  • NP_001362269.1:p.Asn167Lys
  • NP_001362270.1:p.Asn167Lys
  • NP_001362271.1:p.Asn167Lys
  • NP_001362272.1:p.Asn167Lys
  • NP_001362273.1:p.Asn167Lys
  • NP_001362274.1:p.Asn145Lys
  • NP_001362275.1:p.Asn145Lys
  • NP_001362276.1:p.Asn138Lys
  • NP_001362277.1:p.Asn27Lys
  • NP_001362278.1:p.Asn72Lys
  • NP_001362279.1:p.Asn27Lys
  • NP_944493.2:p.Asn167Lys
  • NP_944494.1:p.Asn167Lys
  • NC_000005.9:g.161524817C>A
Protein change:
N138K
Links:
dbSNP: rs1581351046
NCBI 1000 Genomes Browser:
rs1581351046
Molecular consequence:
  • NM_000816.3:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375339.1:c.492C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375340.1:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375341.1:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375342.1:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375343.1:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375344.1:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375345.1:c.435C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375346.1:c.435C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375347.1:c.414C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375348.1:c.81C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375349.1:c.216C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375350.1:c.81C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198903.2:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198904.4:c.501C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Epilepsy, childhood absence 2 (ECA2)
Synonyms:
Febrile seizures, familial, 8
Identifiers:
MONDO: MONDO:0011891; MedGen: C1843244; Orphanet: 64280; OMIM: 607681
Name:
Familial febrile seizures 8 (FEB8)
Synonyms:
CONVULSIONS, FAMILIAL FEBRILE, 8
Identifiers:
MedGen: C1969810; Orphanet: 36387

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000946763Invitaecriteria provided, single submitter
Likely pathogenic
(Dec 10, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000946763.1

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

Description

This sequence change replaces asparagine with lysine at codon 167 of the GABRG2 protein (p.Asn167Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with GABRG2-related disease (Invitae). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 25, 2021

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