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]

Link to SEPIO compliant JSON-LD document

Variant: NM_019863.3:c.610A>T

CA414896830

Gene: F8

Condition: hemophilia A

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 410722b3-4d85-48da-bab9-4d8a259e84d6

Approved on: 2024-06-19

Published on: 2024-07-11

HGVS expressions

NM_019863.3:c.610A>T

NC_000023.11:g.154837638T>A

CM000685.2:g.154837638T>A

NC_000023.10:g.154065913T>A

CM000685.1:g.154065913T>A

NC_000023.9:g.153719107T>A

NG_011403.1:g.190086A>T

NG_033065.1:g.2025A>T

NG_011403.2:g.190086A>T

ENST00000360256.9:c.7015A>T

ENST00000644698.1:c.748A>T

ENST00000330287.10:c.610A>T

ENST00000360256.8:c.7015A>T

NM_000132.3:c.7015A>T

NM_019863.2:c.610A>T

NM_000132.4:c.7015A>T

Likely Pathogenic

PS4 PM2_Supporting PP3

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.7015A>T (Arg2339Trp) variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3). This variant has been reported in at least four probands with severe hemophilia A (>4 probands & 0 gnomAD alleles) meeting phenotypic criteria for F8 (PMID: 30913330, 20331761, 18691168, 18217193). This missense variant has a REVEL score of 0.878 (>0.6). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8: PS4, PP3, PM2_Supporting.

PS4

4 individuals with severe hemophilia A are reported in the literature, meeting criteria for PS4

PM2_Supporting

The c.7015A>T (Arg2339Trp) variant is absent from gnomAD v2.1.1 and v3.1.2

PP3

The Arg2339Trp missense variant meets PP3 with a REVEL score of 0.878 (threshold >0.6)

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