NM_000419.5(ITGA2B):c.1346G>A (p.Gly449Asp) AND Glanzmann thrombasthenia

Clinical significance:Likely pathogenic (Last evaluated: Sep 6, 2020)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000003031.6

Allele description [Variation Report for NM_000419.5(ITGA2B):c.1346G>A (p.Gly449Asp)]

NM_000419.5(ITGA2B):c.1346G>A (p.Gly449Asp)

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.1346G>A (p.Gly449Asp)
Other names:
G418D
HGVS:
  • NC_000017.11:g.44380926C>T
  • NG_008331.1:g.13580G>A
  • NM_000419.5:c.1346G>AMANE SELECT
  • NP_000410.2:p.Gly449Asp
  • LRG_479:g.13580G>A
  • NC_000017.10:g.42458294C>T
  • NM_000419.4:c.1346G>A
  • NM_000419.5(ITGA2B):c.1346G>AMANE SELECT
  • p.Gly449Asp
Protein change:
G449D; GLY418ASP
Links:
OMIM: 607759.0010; dbSNP: rs1598380253
NCBI 1000 Genomes Browser:
rs1598380253
Molecular consequence:
  • NM_000419.5:c.1346G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001397477ClinGen Platelet Disorders Variant Curation Expert Panel,ClinGenreviewed by expert panel
Likely pathogenic
(Sep 6, 2020)
germlinecuration

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

A single amino acid substitution flanking the fourth calcium binding domain of alpha IIb prevents maturation of the alpha IIb beta 3 integrin complex.

Wilcox DA, Wautier JL, Pidard D, Newman PJ.

J Biol Chem. 1994 Feb 11;269(6):4450-7.

PubMed [citation]
PMID:
7508443

Details of each submission

From ClinGen Platelet Disorders Variant Curation Expert Panel,ClinGen, SCV001397477.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

The NM_000419.5:c.1346G>A variant that results in the Gly449Asp amino acid change is reported in one homozygous individual in the literature (PMID: 7508443). It is absent in population databases and is predicted damaging by in-silico tools. Experimental evidence shows the variant results in lack of surface expression of the alphaIIb-beta3 complex. In summary, based on the available evidence at this time, the Gly449Asp variant is classified as likely pathogenic. GT-specific criteria applied: PM2_Supporting, PP3, PP4_moderate, PS3_Supporting and PM3_Supporting.

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

Last Updated: Sep 7, 2021

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