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:c.1036C>T

CA397319681

Gene: GP1BA (HGNC:2811)

Condition: Bernard-Soulier syndrome (MONDO:0009276)

Inheritance Mode: Autosomal recessive inheritance

UUID: 8a0d9655-c2f5-46ca-8bcd-e030daadb9fb

Approved on: 2025-12-16

Published on: 2025-12-16

HGVS expressions

NM_000173.7:c.1036C>T

NC_000017.11:g.4933640C>T

CM000679.2:g.4933640C>T

NC_000017.10:g.4836935C>T

CM000679.1:g.4836935C>T

NC_000017.9:g.4777715C>T

NG_008767.2:g.6346C>T

ENST00000329125.6:c.1036C>T

ENST00000649830.1:c.-888+702G>A

ENST00000329125.5:c.1036C>T

ENST00000611961.1:c.1036C>T

NM_000173.6:c.1036C>T

Likely Pathogenic

PM3 PVS1_Strong PM2_Supporting PP1 PP4

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 1.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Platelet Disorders VCEP

The c.1036C>T (p.Gln346Ter) variant in GP1BA is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove >10% of the protein (PVS1_Strong). At least one patient (Patient 1 in PMID:33553065) with this variant had less than 10% expression of GPIba and GP9 measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome. Additionally, the patient had excessive mucocutaneous bleeding is consistent with Bernard-Soulier syndrome (PP4). This individual was compound heterozygous for this variant and the NM_000173.7:c.1601_1602del (p.Tyr534CysfsTer82) variant, which was classified as Pathogenic by the Clingen PD VCEP. The variants were confirmed in trans through parental testing (1 point, PM3). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_Strong, PM3, PP1, PP4 and PM2_Supporting (VCEP specifications version 1).

PM3

This variant has been detected in at least 1 proband with Bernard-Soulier syndrome (Patient 1 in PMID: 33553065). This individual was compound heterozygous for this variant and the NM_000173.7:c.1601_1602del (p.Tyr534CysfsTer82) variant, which was classified as Pathogenic by the Clingen PD VCEP. The variants were confirmed in trans through parental testing (1 point, PM3).

PVS1_Strong

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PP1

The variant has been reported to segregate in the proband plus 1 additional compound heterozygous BSS affected family members (1 point, PP1).

PP4

At least one patient (Patient 1 in PMID:33553065) with this variant had less than 10% expression of GPIba and GP9 measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome. Additionally, the patient had excessive mucocutaneous bleeding is consistent with Bernard-Soulier syndrome (PP4).

Curation History

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