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NM_000212.3(ITGB3):c.557C>T (p.Pro186Leu) AND Glanzmann thrombasthenia

Germline classification:
Likely benign (1 submission)
Last evaluated:
Feb 8, 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:
RCV003222153.2

Allele description [Variation Report for NM_000212.3(ITGB3):c.557C>T (p.Pro186Leu)]

NM_000212.3(ITGB3):c.557C>T (p.Pro186Leu)

Gene:
ITGB3:integrin subunit beta 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.32
Genomic location:
Preferred name:
NM_000212.3(ITGB3):c.557C>T (p.Pro186Leu)
Other names:
NM_000212.3(ITGB3):c.557C>T; p.Pro186Leu
HGVS:
  • NC_000017.11:g.47284638C>T
  • NG_008332.2:g.35797C>T
  • NM_000212.3:c.557C>TMANE SELECT
  • NP_000203.2:p.Pro186Leu
  • LRG_481t1:c.557C>T
  • LRG_481:g.35797C>T
  • NC_000017.10:g.45362004C>T
  • NC_000017.10:g.45362004C>T
  • NM_000212.2:c.557C>T
Protein change:
P186L
Links:
dbSNP: rs61736876
NCBI 1000 Genomes Browser:
rs61736876
Molecular consequence:
  • NM_000212.3:c.557C>T - 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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003915975ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2-1)		Likely benign
(Feb 8, 2023) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen, SCV003915975.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.557C>T variant in ITGB3 is a missense variant predicted to cause substitution of proline by leucine at amino acid 186. The variant has a high population minor allele frequency in gnomAD v2.1.1 of 0.007131 (178/24960) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.0024). The computational predictor REVEL gives a score of 0.733, which is above the ClinGen PD VCEP PP3 threshold of >0.7 and predicts a damaging effect on ITGB3 function. It is reported to have an association with lower platelet count in an African American cohorts (PMID: 23103231) but has not been reported in a Glanzmann thrombasthenia patient to our knowledge. In summary, this variant meets the criteria to be classified as a variant of unknown significance - conflicting evidence for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, PP3. (VCEP specifications version 2; date of approval 2/2/2023)

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

Last Updated: Oct 13, 2024