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NM_001371727.1(GABRB2):c.775C>T (p.Leu259Phe) AND Intellectual disability

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Feb 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:
RCV003749911.1

Allele description [Variation Report for NM_001371727.1(GABRB2):c.775C>T (p.Leu259Phe)]

NM_001371727.1(GABRB2):c.775C>T (p.Leu259Phe)

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.775C>T (p.Leu259Phe)
HGVS:
  • NC_000005.10:g.161334809G>A
  • NG_047050.1:g.218316C>T
  • NM_000813.3:c.775C>T
  • NM_001371727.1:c.775C>TMANE SELECT
  • NM_021911.3:c.775C>T
  • NP_000804.1:p.Leu259Phe
  • NP_001358656.1:p.Leu259Phe
  • NP_068711.1:p.Leu259Phe
  • NC_000005.9:g.160761816G>A
Protein change:
L259F
Molecular consequence:
  • NM_000813.3:c.775C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371727.1:c.775C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_021911.3:c.775C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Intellectual disability
Synonyms:
Intellectual functioning disability; intellectual disabilities; Intellectual developmental disorder
Identifiers:
MONDO: MONDO:0001071; MeSH: D008607; MedGen: C3714756; Human Phenotype Ontology: HP:0001249

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004428352Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Feb 20, 2023) 		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, SCV004428352.1

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

Description

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 GABRB2 protein function. This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 259 of the GABRB2 protein (p.Leu259Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GABRB2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. 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: Feb 28, 2024