NM_000419.5(ITGA2B):c.2511G>C (p.Gln837His) AND Glanzmann thrombasthenia

Germline classification:: Benign (3 submissions)
Last evaluated:: Oct 17, 2023
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000400716.9

Allele description [Variation Report for NM_000419.5(ITGA2B):c.2511G>C (p.Gln837His)]

NM_000419.5(ITGA2B):c.2511G>C (p.Gln837His)

Gene:

ITGA2B:integrin subunit alpha 2b [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_000419.5(ITGA2B):c.2511G>C (p.Gln837His)

Other names:

NM_000419.5(ITGA2B):c.2511G>C; p.Gln837His

HGVS:

NC_000017.11:g.44375923C>G
NG_008331.1:g.18583G>C
NM_000419.5:c.2511G>CMANE SELECT
NP_000410.2:p.Gln837His
LRG_479t1:c.2511G>C
LRG_479:g.18583G>C
NC_000017.10:g.42453291C>G
NM_000419.3:c.2511G>C
NM_000419.4:c.2511G>C

Protein change:

Q837H

Links:

dbSNP: rs377753373

NCBI 1000 Genomes Browser:

rs377753373

Molecular consequence:

NM_000419.5:c.2511G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glanzmann thrombasthenia
Synonyms:: PLATELET GLYCOPROTEIN IIb-IIIa DEFICIENCY; Thrombasthenia of Glanzmann and Naegeli; Glanzmann thrombasthenia type A; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100326; MedGen: C0040015; Orphanet: 849; OMIM: PS273800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000403363	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV003260901	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Dec 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004190234	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen Platelet ACMG Specifications v2-1)	Benign (Oct 17, 2023)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000403363

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV003260901

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Dec 17, 2023)

germline

clinical testing

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

SCV004190234

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)

Benign
(Oct 17, 2023)

germline

curation

Citation Link

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, curation

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 Illumina Laboratory Services, Illumina, SCV000403363.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003260901.2

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

#	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

From ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen, SCV004190234.1

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

Description

The c.2511G>C variant in ITGA2B is a missense variant predicted to cause substitution of Glutamine by Histidine at amino acid 837 (p.Gln837His). The highest population minor allele frequency in gnomAD v2.1.1 is 0.01740 (530/30456 alleles) in the South Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.197, which is below the ClinGen PD VCEP threshold of <0.25 and predicts no damaging effect on ITGA2B function (BP4). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1 and BP4 (VCEP specifications version 2).

#	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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