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.2947G>A (p.Val983Ile)

CA10568266

368120 (ClinVar)

Gene: F8
Condition: hemophilia A
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 509b91e3-ec2d-417c-9185-c829b28081ef
Approved on: 2024-02-01
Published on: 2024-07-11

HGVS expressions

NM_000132.3:c.2947G>A
NM_000132.3(F8):c.2947G>A (p.Val983Ile)
NC_000023.11:g.154930843C>T
CM000685.2:g.154930843C>T
NC_000023.10:g.154159118C>T
CM000685.1:g.154159118C>T
NC_000023.9:g.153812312C>T
NG_011403.1:g.96881G>A
NG_011403.2:g.96881G>A
ENST00000360256.9:c.2947G>A
ENST00000647125.1:c.*2613G>A
ENST00000360256.8:c.2947G>A
NM_000132.4:c.2947G>A
More

Benign

Met criteria codes 2
BA1 BP4
Not Met criteria codes 1
PS4

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:c.2947G>A (p.Val983Ile) variant is reported at a high MAF of 0.00635 (120/18899 alleles with 31 hemizygotes) in the African subpopulation in gnomAD v2.1.1, meeting BA1 cut-off for F8 (>=0.000333). REVEL and SpliceAI scores of 0.194 and 0.01 meeting the BP4 cut-offs of <0.3 and <0.05, respectively. The variant has not been reported in patients with hemophilia A in the literature or Hemophilia databases, to the best of our knowledge. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency VCEP: BA1, BP4.
Met criteria codes
BA1
The variant is reported at a frequency of 0.00635 (120/18899 alleles with 31 hemizygotes) and at a frequency of 0.006702 (210/31334 alleles with 51 hemizygotes) in the African population in gnomAD v2.1.1 and gnomAD v3, respectively. The MAFs are higher than the BA1 cut-off for F8 (>=0.000333) determined by the CFD-VCEP.
BP4
REVEL score of 0.194 is lower than the threshold for BP4 (<0.3) and SpliceAI score of 0.01 is lower than the threshold for BP4 (<0.05) as determined by the CFD-VCEP.
Not Met criteria codes
PS4
The variant has not been reported in a male patient with Hemophilia A in the literature, to the best of our knowledge. From internal laboratory data: a female individual (presumably heterozygous) with family history of severe HA is reported.
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.