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_000419.5(ITGA2B):c.858C>T (p.Val286=)

CA8603312

323562 (ClinVar)

Gene: ITGA2B (HGNC:3674)

Condition: Glanzmann thrombasthenia (MONDO:0010119)

Inheritance Mode: Autosomal recessive inheritance

UUID: 45d99be7-193f-4943-8eef-03b0407dd395

Approved on: 2024-03-07

Published on: 2024-03-22

HGVS expressions

NM_000419.5(ITGA2B):c.858C>T (p.Val286=)

NM_000419.5:c.858C>T

NC_000017.11:g.44384344G>A

CM000679.2:g.44384344G>A

NC_000017.10:g.42461712G>A

CM000679.1:g.42461712G>A

NC_000017.9:g.39817238G>A

NG_008331.1:g.10162C>T

ENST00000262407.6:c.858C>T

ENST00000648408.1:c.289C>T

ENST00000262407.5:c.858C>T

ENST00000589645.5:n.309C>T

ENST00000591990.5:n.403C>T

ENST00000592075.5:n.227C>T

ENST00000592226.5:n.98C>T

ENST00000592253.5:n.366C>T

ENST00000592944.1:n.540C>T

NM_000419.3:c.858C>T

NM_000419.4:c.858C>T

Likely Benign

BP7 BP4 PM2_Supporting

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

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

NM_000419.5(ITGA2B):c.858C>T (p.Val286=) is a rare synonymous variant. The highest population minor allele frequency in gnomAD v4.0 is 0.00005254 (64/1179956 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant has not been reported in any affected individuals in published literature but has been reported once in a healthy individual as part of a population screen. In silico splicing tools predict this synonymous variant to have no impact on splicing and this is not a highly conserved nucleotide (BP4, BP7). In summary, this variant meets criteria for PM2_supporting, BP4, and BP7; and is therefore classified as likely benign.

BP7

Multiple splicing tools (MaxEntScan, HSF, SpliceAI) predict this variant to have no impact on splicing. The nucleotide is not highly conserved (phyloP score = -1.016)

BP4

Multiple splicing tools (MaxEntScan, HSF, SpliceAI) predict this variant to have no impact on splicing. CADD RawScore 0.711042 PHRED 11.24

PM2_Supporting

The highest population minor allele frequency in gnomAD v4.0 is 0.00005254 (64/1179956 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.