NM_198904.4(GABRG2):c.1108G>T (p.Asp370Tyr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 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:: RCV001321667.8

Allele description [Variation Report for NM_198904.4(GABRG2):c.1108G>T (p.Asp370Tyr)]

NM_198904.4(GABRG2):c.1108G>T (p.Asp370Tyr)

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.1108G>T (p.Asp370Tyr)

HGVS:

NC_000005.10:g.162149293G>T
NG_009290.1:g.86652G>T
NM_000816.3:c.1108G>T
NM_001375339.1:c.1099G>T
NM_001375340.1:c.923-2437G>T
NM_001375341.1:c.1105G>T
NM_001375342.1:c.1105G>T
NM_001375343.1:c.1228G>T
NM_001375344.1:c.1147G>T
NM_001375345.1:c.1042G>T
NM_001375346.1:c.1042G>T
NM_001375347.1:c.1021G>T
NM_001375348.1:c.688G>T
NM_001375349.1:c.823G>T
NM_001375350.1:c.688G>T
NM_198903.2:c.1228G>T
NM_198904.4:c.1108G>TMANE SELECT
NP_000807.2:p.Asp370Tyr
NP_001362268.1:p.Asp367Tyr
NP_001362270.1:p.Asp369Tyr
NP_001362271.1:p.Asp369Tyr
NP_001362272.1:p.Asp410Tyr
NP_001362273.1:p.Asp383Tyr
NP_001362274.1:p.Asp348Tyr
NP_001362275.1:p.Asp348Tyr
NP_001362276.1:p.Asp341Tyr
NP_001362277.1:p.Asp230Tyr
NP_001362278.1:p.Asp275Tyr
NP_001362279.1:p.Asp230Tyr
NP_944493.2:p.Asp410Tyr
NP_944494.1:p.Asp370Tyr
NC_000005.9:g.161576299G>T
NM_000816.3:c.1108G>T

Protein change:

D230Y

Links:

dbSNP: rs1415854808

NCBI 1000 Genomes Browser:

rs1415854808

Molecular consequence:

NM_001375340.1:c.923-2437G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000816.3:c.1108G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375339.1:c.1099G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375341.1:c.1105G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375342.1:c.1105G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375343.1:c.1228G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375344.1:c.1147G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375345.1:c.1042G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375346.1:c.1042G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375347.1:c.1021G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375348.1:c.688G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375349.1:c.823G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375350.1:c.688G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198903.2:c.1228G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198904.4:c.1108G>T - 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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F410_gp087 [Erwinia phage vB_EamP-S6]
F410_gp087 [Erwinia phage vB_EamP-S6]
Gene ID:14013775

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001512507	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001512507

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001512507.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 370 of the GABRG2 protein (p.Asp370Tyr). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with GABRG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1021840). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GABRG2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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