Variant: NM_000419.5(ITGA2B):c.671-13C>T

CA8603374

323564 (ClinVar)

Gene: ITGA2B

Condition: Glanzmann thrombasthenia

Inheritance Mode: Autosomal recessive inheritance

UUID: 73814284-64d8-4dc5-bd4a-9094de6ca3a7

Approved on: 2024-12-17

Published on: 2024-12-17

HGVS expressions

NM_000419.5:c.671-13C>T
NM_000419.5(ITGA2B):c.671-13C>T
NC_000017.11:g.44385089G>A
CM000679.2:g.44385089G>A
NC_000017.10:g.42462457G>A
CM000679.1:g.42462457G>A
NC_000017.9:g.39817983G>A
NG_008331.1:g.9417C>T
ENST00000262407.6:c.671-13C>T
ENST00000648408.1:c.102-13C>T
ENST00000262407.5:c.671-13C>T
ENST00000589645.5:n.122-13C>T
ENST00000591990.5:n.33-13C>T
ENST00000592075.5:n.40-13C>T
ENST00000592226.5:n.39+75C>T
ENST00000592253.5:n.179-13C>T
ENST00000592944.1:n.353-13C>T
NM_000419.3:c.671-13C>T
NM_000419.4:c.671-13C>T

Likely Benign

• Met criteria codes: PM2_Supporting BP7 BP4

• Not Met criteria codes: PP4 BS1 BA1

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.671-13C>T variant in ITGA2B is an intronic variant which located in intron 6. The variant 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 0.328102 (BP4, BP7). The highest population minor allele frequency in gnomAD v4.1.0 is 0.00006666 (4/60004 alleles) in the Admixed American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population, however no cases of the variant segregating in GT patients were found in the literature. 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: BP4, BP7 and PM2_Supporting (VCEP specifications version 2.1.0; date of approval).

Met criteria codes

• PM2_Supporting: The highest population minor allele frequency in gnomAD v4.1.0 is 0.00006666 (4/60004 alleles) in the Admixed American population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting).
• BP7: The c.671-13C>T variant is a intronic variant that is not predicted by SpliceAI to impact splicing (<0.07). In addition, it occurs at a nucleotide that is not conserved as shown by phyloP score of 0.328102 (BP7).
• BP4: The c.671-13C>T variant is a intronic variant that is not predicted by SpliceAI to impact splicing (<0.07).

Not Met criteria codes

• PP4: This variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population, however no cases of the variant segregating in GT patients were found in the literature.
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline