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:c.980T>A

CA414917674

Gene: F8 (HGNC:2157)

Condition: hemophilia A (MONDO:0010602)

Inheritance Mode: X-linked inheritance

UUID: 8c3efe31-9d6b-433e-bd87-e9d10335ed14

Approved on: 2025-05-02

Published on: 2025-05-02

HGVS expressions

NM_000132.3:c.980T>A

NC_000023.11:g.154969360A>T

CM000685.2:g.154969360A>T

NC_000023.10:g.154197635A>T

CM000685.1:g.154197635A>T

NC_000023.9:g.153850829A>T

NG_011403.1:g.58364T>A

NG_011403.2:g.58364T>A

ENST00000360256.9:c.980T>A

ENST00000647125.1:c.*856T>A

ENST00000360256.8:c.980T>A

NM_000132.4:c.980T>A

Likely Pathogenic

PM2_Supporting PP1 PP3 PP4_Moderate PM5

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.980T>A (p.Leu327Gln) variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3) meeting the PM2_Supporting criteria. The missense variant has a REVEL score of 0.868 (>0.6) meeting PP3. The variant has been reported in a proband with severe hemophilia A in the EAHAD Database genotyped through the My Life Our Future program (PP4_Moderate). This information was confirmed by a VCEP member who also reported a similarly affected nephew also found to harbor this variant meeting PP1 criteria. A pathogenic variant, Leu327Val, is reported at the same residue meeting PM5 criteria meeting PM5. In summary, based on the evidence available at this time, the clinical significance of this variant is likely pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8/F9: PM5, PP4_Moderate, PP1, PP3, PM2_Supporting

PM2_Supporting

The c.980T>A (p.Leu327Gln) variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3).

PP1

Proband and nephew with severe hemophilia A and harbor the F8 c.980T>A (p.Leu327Gln) variant.

PP3

The c.980T>A (p.Leu327Gln) missense variant has a REVEL score of 0.868 (>0.6).

PP4_Moderate

1 proband with severe hemophilia A genotyped through the My Life Our Future program.

PM5

p.Leu327Val is a pathogenic variant that has been evaluated by the Coagulation Factor Deficiency VCEP

Curation History

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