Variant: NM_000419.5(ITGA2B):c.2946G>A (p.Val982=)

CA8602501

1803209 (ClinVar)

Gene: ITGA2B

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: 8b2babb0-eaf0-4d97-a6b3-bf5b77d28a63

Approved on: 2023-12-19

Published on: 2023-12-19

HGVS expressions

NM_000419.5:c.2946G>A
NM_000419.5(ITGA2B):c.2946G>A (p.Val982=)
NC_000017.11:g.44374468C>T
CM000679.2:g.44374468C>T
NC_000017.10:g.42451836C>T
CM000679.1:g.42451836C>T
NC_000017.9:g.39807362C>T
NG_008331.1:g.20038G>A
ENST00000262407.6:c.2946G>A
ENST00000648408.1:c.2374+191G>A
ENST00000262407.5:c.2946G>A
ENST00000587295.5:c.253+1365G>A
ENST00000588098.1:c.37+191G>A
ENST00000592462.5:n.2645G>A
NM_000419.3:c.2946G>A
NM_000419.4:c.2946G>A

Likely Benign

• Met criteria codes: BP4 BP7

• Not Met criteria codes: BA1 PM2 BS1

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 c.2946G>A (p.Val982=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing and the nucleotide is only moderately conserved, as shown by phyloP score of 0.703 (BP4, BP7). The highest population minor allele frequency in gnomAD v3.1.2 is 0.0001448 (6/41436 alleles) in the African/African American population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting, so no allele frequency criteria were met. In addition, no cases of the variant segregating with Glanzmann thrombasthenia were found in the literature. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive Glanzmann Thrombasthenia with the following ACMG/AMP applied, as specified by the ClinGen PD VCEP: BP4, BP7 (VCEP specifications version 2.1)

Met criteria codes

• BP4: The c.2946G>A (p.Val982=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (delta scores <=0.05).
• BP7: The c.2946G>A (p.Val982=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing (delta scores <=0.05) and the nucleotide is only moderately conserved, as shown by phyloP score of 0.703.

Not Met criteria codes

• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: The highest population minor allele frequency in gnomAD v3.1.2 is 0.0001448 (6/41436 alleles) in the African/African American population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting.
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline