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]
Link to SEPIO compliant JSON-LD document
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000132.3(F8):c.6046C>T (p.Arg2016Trp)

CA255197

10304 (ClinVar)

Gene: F8
Condition: hemophilia A
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 3d921025-1d2e-41c3-9200-a2d11c4ad044
Approved on: 2024-02-02
Published on: 2024-07-11

HGVS expressions

NM_000132.3:c.6046C>T
NM_000132.3(F8):c.6046C>T (p.Arg2016Trp)
NC_000023.11:g.154902120G>A
CM000685.2:g.154902120G>A
NC_000023.10:g.154130395G>A
CM000685.1:g.154130395G>A
NC_000023.9:g.153783589G>A
NG_011403.1:g.125604C>T
NG_011403.2:g.125604C>T
ENST00000360256.9:c.6046C>T
ENST00000360256.8:c.6046C>T
NM_000132.4:c.6046C>T

Pathogenic

Met criteria codes 4
PS4 PP4_Moderate PM2_Supporting PP3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F8 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Coagulation Factor Deficiency VCEP
The c.6046C>T (p.Arg2016Trp) variant is completely absent from gnomAD v2.1.1 and gnomAD v3 meeting PM2_Supporting. This missense variant has a REVEL score of 0.822 (>0.6) meeting PP3 criteria. More than 46 probands are reported with the variant and moderate-severe hemophilia A in the literature and internal laboratory data (PMID: 29296726, 20102490, 18387975), meeting F8 phenotype criteria. This variant has been associated with discrepant factor VIII activity levels (PMID: 32232366). This variant has also been reported in individuals with a history of inhibitor development to factor replacement therapy (EAHAD database). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8: PS4_Very Strong, PP4_Moderate, PP3, PM2_Supporting.
Met criteria codes
PS4
More than 46 probands are reported with the variant and moderate-severe hemophilia A in the literature and internal laboratory data (PMID: 29296726, 20102490, 18387975), meeting F8 phenotype criteria. The threshold for PS4_Very Strong is met (>8).
PP4_Moderate
Male with severe hemophilia A who had full F8 and F9 gene sequencing and deletion/duplication analysis.
PM2_Supporting
The c.6046C>T (p.Arg2016Trp) variant is completely absent from gnomAD v2.1.1 and gnomAD v3.
PP3
This missense variant has a REVEL score of 0.822 (>0.6) and meets criteria for PP3.
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.