Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000173.7(GP1BA):c.106A>G (p.Arg36Gly)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA8314695

255462 (ClinVar)

Gene: GP1BA

Condition: Bernard-Soulier syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 39bf4fc7-f32a-4b89-a5cd-4074f56d3518

Approved on: 2025-02-11

Published on: 2025-02-12

HGVS expressions

NM_000173.7:c.106A>G

NM_000173.7(GP1BA):c.106A>G (p.Arg36Gly)

NC_000017.11:g.4932710A>G

CM000679.2:g.4932710A>G

NC_000017.10:g.4836005A>G

CM000679.1:g.4836005A>G

NC_000017.9:g.4776785A>G

NG_008767.2:g.5416A>G

ENST00000329125.6:c.106A>G

ENST00000649830.1:c.-888+1632T>C

ENST00000329125.5:c.106A>G

ENST00000611961.1:c.106A>G

NM_000173.6:c.106A>G

Benign

BA1

BP2 BP4 PP3

Evidence Links 0

Expert Panel

Platelet Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Platelet Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GP1BA Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The NM_000173.7(GP1BA):c.106A>G (p.Arg36Gly) missense variant occurs at a frequency too high for disease; the Grpmax filtering allele frequency in gnomAD v4.1 is 0.01679 (based on 1319/75016 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.001; BA1). Therefore this variant is classified as Benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP (specifications version 1).

BA1

The Grpmax filtering allele frequency in gnomAD v4.1 is 0.01679 (based on 1319/75016 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.001), and therefore meets this criterion (BA1).

BP2

BSS patient, in PMID: 24934643, is homozygous for both c.106G>A and c.23_31del, which is considered to be the likely pathogenic variant however has not yet been curated by the PD-VCEP.

BP4

The computational predictor REVEL gives a score of 0.328, which is above the ClinGen PD VCEP threshold of <0.290 and SpliceAI indicated that the variant has no predicted impact on splicing but gives a score of 0.01 for gain of an acceptor site 13bp away.

PP3

The computational predictor REVEL gives a score of 0.328, which is below the ClinGen PD VCEP PP3 threshold of >0.644 and does not predict a damaging effect on GP1BA function. And the computational splicing predictor SpliceAI indicated that the variant has no predicted impact on splicing.

Curation History

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