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.1804C>T (p.Arg602Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA255124

10232 (ClinVar)

Gene: F8

Condition: hemophilia A

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 8d0f7cbb-2982-46ea-b526-c6afd4ec4be3

Approved on: 2024-02-02

Published on: 2024-07-11

HGVS expressions

NM_000132.3:c.1804C>T

NM_000132.3(F8):c.1804C>T (p.Arg602Ter)

NC_000023.11:g.154953991G>A

CM000685.2:g.154953991G>A

NC_000023.10:g.154182266G>A

CM000685.1:g.154182266G>A

NC_000023.9:g.153835460G>A

NG_011403.1:g.73733C>T

NG_011403.2:g.73733C>T

ENST00000360256.9:c.1804C>T

ENST00000647125.1:c.*1680C>T

ENST00000360256.8:c.1804C>T

NM_000132.4:c.1804C>T

Pathogenic

PP4_Moderate PM2_Supporting PVS1 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.1804C>T (p.Arg602Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon in exon 12 and expected to result in nonsense-mediated mRNA decay. This variant is absent from males in gnomAD v2.1.1 and v3.1.1, which meets criteria for PM2_Supporting. More than 25 patients with moderate-severe hemophilia A are reported in the literature and internal laboratory data, meeting criteria for PS4_Very Strong and PP4_Moderate (PMID: 29296726, 18387975, 18691168, 16769589, 8639447, 20331761). 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: PVS1, PS4_Very Strong, PP4_Moderate, PM2_Supporting.

PP4_Moderate

Male with severe hemophilia A who had full F8 and F9 gene sequencing and deletion/duplication analysis through MLOF study.

PM2_Supporting

The variant is absent from males in gnomAD v2.1.1 and v3.1.1

PVS1

The c.1804C>T (p.Arg602Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon in exon 12 and expected to result in nonsense-mediated mRNA decay. Meets PVS1 criteria

PS4

Numerous patients with moderate-severe hemophilia A are reported in the literature and internal laboratory data, meeting criteria for PS4_Very Strong (>8 probands).

Curation History

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