ClinVar Miner

Submissions for variant NM_000132.3(F8):c.748A>G (p.Met250Val) (rs781943293)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001002350 SCV001160254 uncertain significance Hereditary factor VIII deficiency disease 2019-01-31 criteria provided, single submitter clinical testing The F8 c.748A>G; p.Met250Val variant (rs781943293), to our knowledge, is not described in the medical literature or in gene-specific databases. It is observed in the Latino population at an overall frequency of 0.043% (12/28057 alleles, 3 hemizygotes) in the Genome Aggregation Database. The methionine at codon 250 is weakly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. Additionally, another variant at this position (c.6749T>G; p.Met250Arg) has been described in two relatives with mild hemophilia A (Guillet 2006). However, due to the lack of clinical and functional data regarding the p.Met250Val variant, its clinical significance cannot be determined with certainty. REFERENCES Guillet B et al. Detection of 95 novel mutations in coagulation factor VIII gene F8 responsible for hemophilia A: results from a single institution. Hum Mutat. 2006 Jul;27(7):676-85.
Illumina Clinical Services Laboratory,Illumina RCV001002350 SCV001331928 likely benign Hereditary factor VIII deficiency disease 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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