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NM_198904.4(GABRG2):c.365A>G (p.Tyr122Cys) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 10, 2020
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:
RCV000526215.8

Allele description [Variation Report for NM_198904.4(GABRG2):c.365A>G (p.Tyr122Cys)]

NM_198904.4(GABRG2):c.365A>G (p.Tyr122Cys)

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.365A>G (p.Tyr122Cys)
HGVS:
  • NC_000005.10:g.162097675A>G
  • NG_009290.1:g.35034A>G
  • NM_000816.3:c.365A>G
  • NM_001375339.1:c.356A>G
  • NM_001375340.1:c.365A>G
  • NM_001375341.1:c.365A>G
  • NM_001375342.1:c.365A>G
  • NM_001375343.1:c.365A>G
  • NM_001375344.1:c.365A>G
  • NM_001375345.1:c.299A>G
  • NM_001375346.1:c.299A>G
  • NM_001375347.1:c.278A>G
  • NM_001375348.1:c.-31-25A>G
  • NM_001375349.1:c.80A>G
  • NM_001375350.1:c.-31-25A>G
  • NM_198903.2:c.365A>G
  • NM_198904.4:c.365A>GMANE SELECT
  • NP_000807.2:p.Tyr122Cys
  • NP_001362268.1:p.Tyr119Cys
  • NP_001362269.1:p.Tyr122Cys
  • NP_001362270.1:p.Tyr122Cys
  • NP_001362271.1:p.Tyr122Cys
  • NP_001362272.1:p.Tyr122Cys
  • NP_001362273.1:p.Tyr122Cys
  • NP_001362274.1:p.Tyr100Cys
  • NP_001362275.1:p.Tyr100Cys
  • NP_001362276.1:p.Tyr93Cys
  • NP_001362278.1:p.Tyr27Cys
  • NP_944493.2:p.Tyr122Cys
  • NP_944494.1:p.Tyr122Cys
  • NC_000005.9:g.161524681A>G
Protein change:
Y100C
Links:
dbSNP: rs1554097875
NCBI 1000 Genomes Browser:
rs1554097875
Molecular consequence:
  • NM_001375348.1:c.-31-25A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001375350.1:c.-31-25A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000816.3:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375339.1:c.356A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375340.1:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375341.1:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375342.1:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375343.1:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375344.1:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375345.1:c.299A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375346.1:c.299A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375347.1:c.278A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375349.1:c.80A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198903.2:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198904.4:c.365A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000645967Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Feb 10, 2020) 		germlineclinical testing

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

Help

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, SCV000645967.6

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

Description

In summary, this variant has uncertain impact on GABRG2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with a GABRG2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 122 of the GABRG2 protein (p.Tyr122Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine.

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

Last Updated: Mar 5, 2024