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_000132.3(F8):c.1086G>A (p.Ala362=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10568504

368124 (ClinVar)

Gene: F8

Condition: hemophilia A

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: da8548aa-7cf8-42ab-aee5-ecd433fa0ed5

Approved on: 2024-02-01

Published on: 2024-07-11

HGVS expressions

NM_000132.3:c.1086G>A

NM_000132.3(F8):c.1086G>A (p.Ala362=)

NC_000023.11:g.154966611C>T

CM000685.2:g.154966611C>T

NC_000023.10:g.154194886C>T

CM000685.1:g.154194886C>T

NC_000023.9:g.153848080C>T

NG_011403.1:g.61113G>A

NG_011403.2:g.61113G>A

ENST00000360256.9:c.1086G>A

ENST00000647125.1:c.*962G>A

ENST00000360256.8:c.1086G>A

NM_000132.4:c.1086G>A

Benign

BA1 BP7 BP4

PS4

Evidence Links 0

Expert Panel

Coagulation Factor Deficiency VCEP

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.1086G>A (p.Ala362=) variant is reported at an MAF of 0.03761 (713/18957 alleles) in the African/African-American population in gnomAD v2.1.1 with 201 hemizygotes, meeting BA1 criteria of MAF > 0.000333. SpliceAI predicts no impact on splicing with scores of 0, and the nucleotide is not conserved based on agreement between PhyloP (-2.25) and PhastCons (0) scores meeting BP4 and BP7. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8/F9: BA1, BP4, BP7.

BA1

BP7

The c.1086G>A (p.Ala362=) synonymous variant is predicted to have no impact on splicing based on spliceAI prediction with a score of 0, and the nucleotide is not conserved based on agreement between PhyloP (-2.25) and PhastCons (0) scores.

BP4

SpliceAI predicts no impact on splicing with scores of 0, meeting criteria for BP4.

PS4

The variant is reported in at least 3 patients with Hemophilia A from the EAHAD database and internal laboratory data, but alternate pathogenic variants were observed in all these patients. PS4 is not considered when BA1 is met.

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.