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]

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Variant: NM_000132.3(F8):c.6769A>G (p.Met2257Val)

CA343869

41001 (ClinVar)

Gene: F8

Condition: hemophilia A

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: a3bad0b0-ae42-494c-80b7-726b05fbbd9e

Approved on: 2024-02-01

Published on: 2024-07-11

HGVS expressions

NM_000132.3:c.6771A>G

NM_000132.3:c.6769A>G

NM_000132.3(F8):c.6769A>G (p.Met2257Val)

NC_000023.11:g.154860563T>C

CM000685.2:g.154860563T>C

NC_000023.10:g.154088838T>C

CM000685.1:g.154088838T>C

NC_000023.9:g.153742032T>C

NG_011403.1:g.167161A>G

NG_011403.2:g.167161A>G

ENST00000360256.9:c.6769A>G

ENST00000644698.1:c.502A>G

ENST00000330287.10:c.364A>G

ENST00000360256.8:c.6769A>G

NM_019863.2:c.364A>G

NM_000132.4:c.6769A>G

NM_019863.3:c.364A>G

Benign

BP4 BA1

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 missense variant, NM_000132.3(F8):c.6769A>G (p.Met2257Val), is reported at an MAF of 0.2418 (4578/18936 with 1245 hemizygotes) in the African population in gnomAD v2.1.1. A REVEL score of 0.292 and SpliceAI score of 0 meets BP4 cut-off (respective thresholds <0.3 and <0.05). 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: BA1, BP4.

BP4

REVEL score of 0.292 meets BP4 cut-off (threshold <0.3). SpliceAI score is 0, which meets the <0.05 cut-off.

BA1

The Met2257Val variant is reported at the highest MAF in the African population in gnomAD v2.1.1 at a frequency of 0.2418 (4578/18936 with 1245 hemizygotes). in gnomAD v3, it is reported at a frequency of 0.2352 (7295/31011 alleles with 1897 hemizygotes) in the African population. Both MAFs meet F8 criteria for BA1 >= 0.000333

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