Variant: NM_000212.3(ITGB3):c.1641C>T (p.Cys547=)

CA8623301

696833 (ClinVar)

Gene: ITGB3

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: 8fdb27fe-755a-4e0b-88f8-d28aedee3289

Approved on: 2022-04-13

Published on: 2022-06-12

HGVS expressions

NM_000212.3:c.1641C>T
NM_000212.3(ITGB3):c.1641C>T (p.Cys547=)
NC_000017.11:g.47292519C>T
CM000679.2:g.47292519C>T
NC_000017.10:g.45369885C>T
CM000679.1:g.45369885C>T
NC_000017.9:g.42724884C>T
NG_008332.2:g.43678C>T
ENST00000559488.7:c.1641C>T
ENST00000559488.5:c.1641C>T
ENST00000560629.1:n.1606C>T
NM_000212.2:c.1641C>T

Benign

• Met criteria codes: BP4 BA1

• Not Met criteria codes: BP7

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Platelet Disorders VCEP

The ITGB3 synonymous variant NM_000212.3:c.1641C>T is common in control population databases, occurring at a frequency of 0.3015% in the East Asian population of gnomAD v2.1.1. The c.1641C>T (p.Cys547=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4). In summary, this variant meets the criteria to be classified as benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4. (VCEP specifications version 2; date of approval 04/07/2022)

Met criteria codes

• BP4: The c.1641C>T (p.Cys547=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (BP4).
• BA1: The highest population minor allele frequency in gnomAD v2.1.1 is 0.003015 (60/19902 alleles) in East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.0024) for BA1, and therefore meets this criterion (BA1).

Not Met criteria codes

• BP7: The c.1641C>T (p.Cys547=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing. However, it occurs at a nucleotide that is conserved as shown by phyloP score of -0.73, preventing application of BP7.