Submissions for variant NM_000212.3(ITGB3):c.749A>G (p.Asp250Gly)

dbSNP: rs1057518838

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	RCV003221968	SCV003916003	likely pathogenic	Glanzmann thrombasthenia	2023-04-06	reviewed by expert panel	curation	The c.749A>G variant in ITGB3 is a missense variant predicted to cause substitution of aspartic acid by glycine at amino acid 250. The variant has been reported in at least one patient (Glanzmann Patient, "HEMOSTAZA SKOZI KLINIČNE PRIMERE" August 2022) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). This individual is compound heterozygous for this variant and pathogenic variant c.1699C>T (p.Gln567Ter) (PM3). The variant is absent from gnomAD (PM2_supporting). The computational predictor REVEL gives a score of 0.988, which is above the ClinGen PD VCEP PP3 threshold of >0.7 and predicts a damaging effect on ITGB3 function. In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_Supporting, PP3, PP4_moderate, and PM3. (VCEP specifications version 2)
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415046	SCV000492699	likely pathogenic	Abnormal bleeding; Prolonged bleeding time	2015-11-06	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001197460	SCV001368207	likely pathogenic	Platelet-type bleeding disorder 16	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic.