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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000212.3(ITGB3):c.670G>A (p.Asp224Asn)

CA8623019

890135 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 72a5cc2f-9789-4709-bae7-a4fc32a212a1

HGVS expressions

NM_000212.3:c.670G>A

NM_000212.3(ITGB3):c.670G>A (p.Asp224Asn)

NC_000017.11:g.47286315G>A

CM000679.2:g.47286315G>A

NC_000017.10:g.45363681G>A

CM000679.1:g.45363681G>A

NC_000017.9:g.42718680G>A

NG_008332.2:g.37474G>A

ENST00000559488.7:c.670G>A

ENST00000559488.5:c.670G>A

ENST00000560629.1:c.635G>A

ENST00000571680.1:c.670G>A

NM_000212.2:c.670G>A

Uncertain Significance

PM2 BS1 BA1 PP4 PP3

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2.1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The c.670G>A variant in ITGB3 is a missense variant predicted to cause substitution of Aspartic Acid by Asparagine at amino acid 224 (p.Asp224Asn). This variant was observed as part of a predisposition screen in an ostensibly healthy population by Illumina. No ACMG/AMP criteria could be applied to this variant. In summary, this variant meets the criteria to be classified as Uncertain significance - insufficient evidence for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP (VCEP specifications version 2).

PM2

The highest population minor allele frequency in gnomAD v2.1.1 is 0.0009030 (32/35438 alleles) in the Latino/Admixed American population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting. Combined gnomADv2.1.1 and gnomADv3.2.1 (non-v2) the Latino/Admixed American MAF is 0.001342 (66/49180 alleles) which is still intermediate.

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

This variant was observed as part of a predisposition screen in an ostensibly healthy population by Illumina.

PP3

The computational predictor REVEL gives a score of 0.501, which is below the ClinGen PD VCEP PP3 threshold of >0.7 and does not predict a damaging effect on ITGB3 function. And the computational splicing predictor SpliceAI indicated that the variant has no impact on splicing.

Approved on: 2023-09-07

Published on: 2023-09-21

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