Variant: NM_000212.2(ITGB3):c.1143A>C (p.Val381=)

CA8623175

255535 (ClinVar)

Gene: ITGB3

Condition: Glanzmann's thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: d02c575c-86f4-4ca9-8969-b3dfc1bcfe3c

Approved on: 2020-09-04

Published on: 2021-01-22

HGVS expressions

NM_000212.2:c.1143A>C
NM_000212.2(ITGB3):c.1143A>C (p.Val381=)
NM_000212.3:c.1143A>C
ENST00000559488.5:c.1143A>C
ENST00000560629.1:n.1108A>C
ENST00000571680.1:c.1143A>C
NC_000017.11:g.47290971A>C
CM000679.2:g.47290971A>C
NC_000017.10:g.45368337A>C
CM000679.1:g.45368337A>C
NC_000017.9:g.42723336A>C
NG_008332.2:g.42130A>C

Benign

• Met criteria codes: BA1

• Not Met criteria codes: BP2 BS2

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Platelet Disorders VCEP

The ITGB3 synonymous variant NM_000212.2:c.1143A>C is very common in control population databases, with an overall allele frequency of 0.38777 in gnomAD v2.1.1. Note that initial reports of variation at this nucleotide position referred to the current reference allele as the variant at this position (c.1143C>A; PMID: 8878424, PMID: 20020534, and PMID: 25728920), however this reported "variant" is now considered the reference allele. In summary, this variant meets criteria to be classified as benign for GT. GT-specific criteria applied: BA1.

Met criteria codes

• BA1: This variant is very common in control population databases. It was observed in gnomAD v2.1.1 with a MAF in the East Asian population of 0.58573 (11683/19946 alleles) and an overall allele frequency of 0.38777 (109650/282770 alleles). Furthermore, gnomAD v2.1.1 reported this variant in homozygosity in 22230 individuals. This frequency is well above the VCEP-established threshold of 0.0024, meeting the criterion to apply BA1.

Not Met criteria codes

• BP2: This variant was reported in heterozygosity in one individual (F1P1, PMID: 30325339) in combination with 3 other ITGB3 variants (c.176T>C (p.Leu59Pro), c.1545G>A (p.Arg515Arg), and c.1035+102G>C), all in the heterozygous state. However, the phase of these variants was not confirmed. Initial reports of variation at this nucleotide position referred to the current reference allele as the variant at this position (i.e. "variants" originally reported as c.1143C>A are now considered the reference allele). Therefore, reports of the "c.1143C>A variant" in at least two individuals (patient RS in PMID: 8878424 and GT50 in PMID: 25728920) in cis with ITGB3 variant c.1260G>A, which is provisionally classified as likely pathogenic by the Platelet Disorders VCEP, were not used to satisfy BP2.
• BS2: Although this variant has been reported in the homozygous state in 22230 individuals in gnomAD v2.1.1, a cohort of reportedly healthy individuals, phenotypic data for these individuals is not available.