Variant: NM_000212.3(ITGB3):c.1764G>C (p.Thr588=)

CA500435385

759891 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: 2f28b2ef-6dbb-4c0a-983c-e5fd00c5c0e5

Approved on: 2024-03-07

Published on: 2024-03-08

HGVS expressions

NM_000212.3:c.1764G>C
NM_000212.3(ITGB3):c.1764G>C (p.Thr588=)
NC_000017.11:g.47299381G>C
CM000679.2:g.47299381G>C
NC_000017.10:g.45376747G>C
CM000679.1:g.45376747G>C
NC_000017.9:g.42731746G>C
NG_008332.2:g.50540G>C
ENST00000696963.1:c.1764G>C
ENST00000559488.7:c.1764G>C
ENST00000559488.5:c.1764G>C
ENST00000560629.1:c.1729G>C
NM_000212.2:c.1764G>C

Likely Benign

• Met criteria codes: BP7 BP4 PM2_Supporting

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

The NM_000212.3(ITGB3):c.1764G>C (p.Thr588=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4). In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of -8.25384 (BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006153 (1/16252 alleles) in the African American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). Due to conflicting evidence, this variant is classified as likely benign for autosomal recessive Glanzmann thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD-VCEP: BP7, BP4, PM2_Supporting (VCEP specifications version 2.1).

Met criteria codes

• BP7: The c.1764G>C (p.Thr588=) 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 -8.25384 (BP7).
• BP4: The c.1764G>C (p.Thr588=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4).
• PM2_Supporting: The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006153 (1/16252 alleles) in the African American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).