NM_001371727.1(GABRB2):c.737T>C (p.Ile246Thr) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 24, 2017
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:: RCV000478537.1

Allele description [Variation Report for NM_001371727.1(GABRB2):c.737T>C (p.Ile246Thr)]

NM_001371727.1(GABRB2):c.737T>C (p.Ile246Thr)

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.737T>C (p.Ile246Thr)

HGVS:

NC_000005.10:g.161334847A>G
NG_047050.1:g.218278T>C
NM_000813.3:c.737T>C
NM_001371727.1:c.737T>CMANE SELECT
NM_021911.3:c.737T>C
NP_000804.1:p.Ile246Thr
NP_001358656.1:p.Ile246Thr
NP_068711.1:p.Ile246Thr
NP_068711.1:p.Ile246Thr
NC_000005.9:g.160761854A>G
NM_021911.2:c.737T>C

Protein change:

I246T

Links:

dbSNP: rs1064793551

NCBI 1000 Genomes Browser:

rs1064793551

Molecular consequence:

NM_000813.3:c.737T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371727.1:c.737T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_021911.3:c.737T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566400	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Feb 24, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566400

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Feb 24, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000566400.3

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

Description

The I246T variant in the GABRB2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. However, I246T has been observed at GeneDx as a de novo variant with confirmed parentage in unrelated patients with infantile-onset epilepsy and developmental delay. The I246T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I246T variant is a non-conservative amino acid substitution that occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret I246T as a pathogenic variant.

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

Last Updated: Apr 23, 2022

ClinVar

Relating variation to medicine