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.4121_4124del (p.Ile1374fs)

CA255148

10256 (ClinVar)

Gene: F8
Condition: hemophilia A
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: eec8143e-0a98-4734-9318-ab3c2cdc0c32
Approved on: 2024-02-09
Published on: 2024-07-11

HGVS expressions

NM_000132.3:c.4121_4124del
NM_000132.3(F8):c.4121_4124del (p.Ile1374fs)
NC_000023.11:g.154929669_154929672del
CM000685.2:g.154929669_154929672del
NC_000023.10:g.154157944_154157947del
CM000685.1:g.154157944_154157947del
NC_000023.9:g.153811138_153811141del
NG_011403.1:g.98055_98058del
NG_011403.2:g.98055_98058del
ENST00000360256.9:c.4121_4124del
ENST00000360256.8:c.4121_4124del
NM_000132.4:c.4121_4124del
More

Pathogenic

Met criteria codes 3
PVS1 PS4 PM2_Supporting

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(F8):c.4121_4124del (p.Ile1374fs) variant is a frameshift variant that is predicted to introduce a premature stop codon in exon 14 and expected to result in nonsense-mediated mRNA decay, which meets PVS1. It is reported in at least 7 patients with moderate or severe hemophilia A in the literature reviewed (PMID: 22103590, 20102490, 8307558, 9829908, 17498081, 20028422) meeting PS4_Very strong. There are additional probands with the variant reported in the EAHAD database, recorded from the literature. The variant is absent from gnomAD v2.1.1 and v3, which meets PM2_Supporting. 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: PVS1, PS4, PM2_Supporting.
Met criteria codes
PVS1
The variant is a 4-bp deletion that results in a frameshift, Ile1374ThrfsTer49, with termination occurring in exon 14/26, expected to cause NMD.
PS4
6 patients with severe (PMID: 22103590, 20102490, 8307558, 9829908, 17498081) and 1 patient with moderate (20028422) hemophilia A are reported with the 4-bp deletion leading to the frameshift variant, Ile1374ThrfsTer49 in the literature and meet F8-phenotype criteria. PS4 is applied.
PM2_Supporting
The c.4121_4124del (p.Ile1374fs) variant is completely absent in population databases (gnomAD v2.1.1/gnomAD v3).
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.