Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000212.2(ITGB3):c.900T>C (p.His300=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA8623076

435536 (ClinVar)

Gene: ITGB3

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 98fe3613-1331-4d1e-b35d-cac06ddfb34a

Approved on: 2021-05-07

Published on: 2021-08-19

HGVS expressions

NM_000212.2:c.900T>C

NM_000212.2(ITGB3):c.900T>C (p.His300=)

ENST00000559488.7:c.900T>C

ENST00000559488.5:c.900T>C

ENST00000560629.1:n.865T>C

ENST00000571680.1:c.900T>C

NM_000212.3:c.900T>C

NC_000017.11:g.47287192T>C

CM000679.2:g.47287192T>C

NC_000017.10:g.45364558T>C

CM000679.1:g.45364558T>C

NC_000017.9:g.42719557T>C

NG_008332.2:g.38351T>C

Likely Benign

BS1 BP7 BP4

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000212.2(ITGB3):c.900T>C (p.His300=) synonymous variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population but has not been reported in a GT patient. It is not predicted to have an impact on splicing. The variant occurs at an allele frequency greater than expected for the disorder with a MAF of 0.003664 (38/10370 alleles) in the gnomAD Ashkenazi Jewish population.In summary, this variant meets criteria to be classified as Likely Benign for GT. GT-specific criteria applied: BS1, BP4, and BP7

BS1

The overall allele frequency in gnomAD is 0.0002512 with a MAF of 0.003664 (38/10370 alleles) in the Ashkenazi Jewish population. This is above the BA1 threshold of >0.0024, however because this is an inbred population the more conservative BS1 criterion was applied. The next highest MAF is 0.0002559 (33/128932 alleles) in the non-Finnish European population which is an intermediate allele frequency, below the BS1 threshold of >0.00158 but above the PM2 threshold of <0.0001.

BP7

The synonymous variant is not predicted to impact the splice consensus sequence, according to MaxEntScan or HSF. The nucleotide is not highly conserved (phyloP score 0.147772).

BP4

The synonymous variant is not predicted to impact the splice consensus sequence, according to MaxEntScan or HSF. CADD RawScore 0.389114 PHRED 5.305

Curation History

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