Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000173.7(GP1BA):c.1232C>T (p.Pro411Leu)

CA8314930

255464 (ClinVar)

Gene: GP1BA
Condition: Bernard-Soulier syndrome
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 690785fc-52f7-46da-8aaf-ac302a947877
Approved on: 2025-02-11
Published on: 2025-02-12

HGVS expressions

NM_000173.7:c.1232C>T
NM_000173.7(GP1BA):c.1232C>T (p.Pro411Leu)
NC_000017.11:g.4933836C>T
CM000679.2:g.4933836C>T
NC_000017.10:g.4837131C>T
CM000679.1:g.4837131C>T
NC_000017.9:g.4777911C>T
NG_008767.2:g.6542C>T
ENST00000329125.6:c.1232C>T
ENST00000649830.1:c.-888+506G>A
ENST00000329125.5:c.1232C>T
ENST00000611961.1:c.1232C>T
NM_000173.6:c.1232C>T
More

Benign

Met criteria codes 2
BP4 BA1
Not Met criteria codes 4
BS1 PM2 PM3 PP4

Evidence Links 0

Expert Panel

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.1232C>T variant in GP1BA is a missense variant predicted to cause substitution of Proline by Leucine at amino acid 411 (p.Pro411Leu). The Grpmax filtering allele frequency in gnomAD v4.1 is 0.007836 (based on 54/5424) in the Middle Eastern population, which is higher than the ClinGen PD VCEP threshold (>0.001), and therefore meets BA1. The computational predictor REVEL gives a score of 0.223, which is below the ClinGen PD VCEP threshold of <0.290 and predicts no damaging effect on GP1BA function and the SpliceAI score is zero (BP4). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1 and BP4 (VCEP specifications version 1).
Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.223, which is below the ClinGen PD VCEP threshold of <0.290 and predicts no damaging effect on GP1BA function and the SpliceAI score is zero (BP4).
BA1
The Grpmax filtering allele frequency in gnomAD v4.1 is 0.007836 (based on 54/5424) in the Middle Eastern population, which is higher than the ClinGen PD VCEP threshold (>0.001), and therefore meets this criterion (BA1).
Not Met criteria codes
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Internal patient also carries the GP1BB c. 127G>T Gly43Trp and GP1BB c.176A>C Glu59Ala variants, but no other GP1BA variant.
PP4
Internal patient also carries the GP1BB c. 127G>T Gly43Trp, GP1BB c.176A>C Glu59Ala variants. Multiple CBC studies have identified mild thrombocytopenia, with testing on 9/28/2016, 10/25/2016, and 9/23/2021 showing platelet counts of 113 K/CUMM, 98 K /CUMM and 104 K/CUMM and MPV of 12.3 fL, 12.1 fL, and 14.1 fL respectively. On a sample from 1/18/22 there was normal platelet aggregation and ATP release. Testing on a sample from 10/21/21 showed normal platelet glycoprotein testing with GPIIb of 143%, GPIIIa of 134%, GPIX of 80% and GPIb-alpha of 110% and platelet TEM showed a normal mean dense body count of 3.0 dense granules/platelet with increased large and round platelets
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.