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NM_001371727.1(GABRB2):c.373G>A (p.Asp125Asn) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 23, 2024
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:
RCV004621748.1

Allele description [Variation Report for NM_001371727.1(GABRB2):c.373G>A (p.Asp125Asn)]

NM_001371727.1(GABRB2):c.373G>A (p.Asp125Asn)

Gene:
GABRB2:gamma-aminobutyric acid type A receptor subunit beta2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q34
Genomic location:
Preferred name:
NM_001371727.1(GABRB2):c.373G>A (p.Asp125Asn)
HGVS:
  • NC_000005.10:g.161459709C>T
  • NG_047050.1:g.93416G>A
  • NM_000813.3:c.373G>A
  • NM_001371727.1:c.373G>AMANE SELECT
  • NM_021911.2:c.373G>A
  • NM_021911.3:c.373G>A
  • NP_000804.1:p.Asp125Asn
  • NP_001358656.1:p.Asp125Asn
  • NP_068711.1:p.Asp125Asn
  • NC_000005.9:g.160886715C>T
Protein change:
D125N
Molecular consequence:
  • NM_000813.3:c.373G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371727.1:c.373G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021911.3:c.373G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005120232Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 23, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.

Hamdan FF, Myers CT, Cossette P, Lemay P, Spiegelman D, Laporte AD, Nassif C, Diallo O, Monlong J, Cadieux-Dion M, Dobrzeniecka S, Meloche C, Retterer K, Cho MT, Rosenfeld JA, Bi W, Massicotte C, Miguet M, Brunga L, Regan BM, Mo K, Tam C, et al.

Am J Hum Genet. 2017 Nov 2;101(5):664-685. doi: 10.1016/j.ajhg.2017.09.008.

PubMed [citation]
PMID:
29100083
PMCID:
PMC5673604

Whole-exome sequencing in adult patients with developmental and epileptic encephalopathy: It is never too late.

Minardi R, Licchetta L, Baroni MC, Pippucci T, Stipa C, Mostacci B, Severi G, Toni F, Bergonzini L, Carelli V, Seri M, Tinuper P, Bisulli F.

Clin Genet. 2020 Nov;98(5):477-485. doi: 10.1111/cge.13823. Epub 2020 Sep 1.

PubMed [citation]
PMID:
32725632

Details of each submission

From Ambry Genetics, SCV005120232.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.373G>A (p.D125N) alteration is located in exon 5 (coding exon 4) of the GABRB2 gene. This alteration results from a G to A substitution at nucleotide position 373, causing the aspartic acid (D) at amino acid position 125 to be replaced by an asparagine (N). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was reported as a de novo occurrence in multiple individuals with seizures, developmental delay, and other clinical features consistent with GABRB2-related developmental and epileptic encephalopathy (Hamdan, 2017; DECIPHER). Another alteration at the same codon, c.373G>C (p.D125H), has been detected in an individual in a cohort of adults with developmental and epileptic encephalopathy (Minardi, 2020). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). This alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: Sep 29, 2024