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 computer assertion could be determined for this classification!

Variant: NM_000132.3(F8):c.6744G>T (p.Trp2248Cys)

CA255218

10327 (ClinVar)

Gene: F8
Condition: hemophilia A
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: c1d2fdde-4edc-4ef1-abe6-0b2c9a311eb6
Approved on: 2024-02-02
Published on: 2024-07-11

HGVS expressions

NM_000132.3:c.6744G>T
NM_000132.3(F8):c.6744G>T (p.Trp2248Cys)
NC_000023.11:g.154860588C>A
CM000685.2:g.154860588C>A
NC_000023.10:g.154088863C>A
CM000685.1:g.154088863C>A
NC_000023.9:g.153742057C>A
NG_011403.1:g.167136G>T
NG_011403.2:g.167136G>T
ENST00000360256.9:c.6744G>T
ENST00000644698.1:c.477G>T
ENST00000330287.10:c.339G>T
ENST00000360256.8:c.6744G>T
NM_019863.2:c.339G>T
NM_000132.4:c.6744G>T
NM_019863.3:c.339G>T
More

Pathogenic

Met criteria codes 3
PM2_Supporting PS4 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 NM_000132.3(F8):c.6744G>T (p.Trp2248Cys) is reported in at least 19 patients with mild, moderate or severe hemophilia A in the literature reviewed (PMID: 17222201, 18691168, 15921397, 1301932, 17610560). There are several additional probands with the variant reported in the EAHAD database, recorded from the literature and unpublished sources. There are also individuals reported with a history of inhibitor development to factor VIII replacement therapy (EAHAD/CDC Champs Databases). The variant is absent from gnomAD v2.1.1 and v3 meeting PM2_Supporting. This missense variant has a REVEL score of 0.925 (>0.6), meeting criteria for PP3. 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/F9: PS4_Very Strong, PP3, PM2_Supporting.
Met criteria codes
PM2_Supporting
The c.6744G>T (p.Trp2248Cys) variant is completely absent from population databases (gnomAD v2.1.1/gnomAD v3)
PS4
At least 19 individuals who meet F8 phenotype criteria with mild-severe hemophilia A are reported in the literature (PMID: 17222201, 18691168, 15921397, 1301932, 17610560), meeting PS4_Very Strong.
PP3
The c.6744G>T (p.Trp2248Cys) missense variant has a REVEL score of 0.925 (>0.6)
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.