Submissions for variant NM_019616.4(F7):c.748G>A (p.Asp250Asn)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetics and Molecular Pathology, SA Pathology	RCV002466855	SCV002761675	likely pathogenic	Congenital factor VII deficiency	2022-05-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331370	SCV004037672	uncertain significance	not specified	2023-08-29	criteria provided, single submitter	clinical testing	Variant summary: F7 c.814G>A (p.Asp272Asn) results in a conservative amino acid change located in the Serine proteases, trypsin domain (IPR001254) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.2e-05 in 239956 control chromosomes in the gnomAD database, including one homozygotes, suggesting a benign role for this variant. c.814G>A has been reported in the literature in a heterozygous individual affected with easy bruising (Herrmann_2009). This report does not provide unequivocal conclusions about association of the variant with Congenital factor VII deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 18976247). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.