Variant: NM_000212.3(ITGB3):c.1089C>T (p.Ser363=)

CA8623144

738411 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: 9c3fc281-f6a3-4001-9b42-4de1c55681a9

Approved on: 2024-03-07

Published on: 2024-03-08

HGVS expressions

NM_000212.3:c.1089C>T
NM_000212.3(ITGB3):c.1089C>T (p.Ser363=)
NC_000017.11:g.47290238C>T
CM000679.2:g.47290238C>T
NC_000017.10:g.45367604C>T
CM000679.1:g.45367604C>T
NC_000017.9:g.42722603C>T
NG_008332.2:g.41397C>T
ENST00000696963.1:c.1089C>T
ENST00000559488.7:c.1089C>T
ENST00000559488.5:c.1089C>T
ENST00000560629.1:c.1054C>T
ENST00000571680.1:c.1089C>T
NM_000212.2:c.1089C>T

Likely Benign

• Met criteria codes: PM2_Supporting BP7 BP4

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

Evidence submitted by expert panel

Platelet Disorders VCEP

After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.1089C>T (p.Ser363=), no individuals with Glanzmann thrombasthenia were reported with the variant. The variant has a low minor allele frequency of 0.00008673 (3/34592 alleles) in the Latino population in gnomAD, which is less than <0.0001 and thus meets PM2_supporting. In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing and a PhyloP score of -0.294 shows that the nucleotide position is not highly conserved (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PM2_supprorting, BP4, and BP7 (PD VCEP specifications version 2.1).

Met criteria codes

• PM2_Supporting: The highest population minor allele frequency in gnomAD v2.1.1 is 0.00008673 (3/34592 alleles) in the Latino population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).
• BP7: The c.1089C>T (p.Ser363=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of -.294 (BP7).
• BP4: The c.1089C>T (p.Ser363=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4).