Submissions for variant NM_021871.4(FGA):c.1366A>G (p.Thr456Ala)

gnomAD frequency: 0.00262  dbSNP: rs2070031

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000964973	SCV001112228	benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001145722	SCV001306415	likely benign	Congenital afibrinogenemia	2018-01-13	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.
Illumina Laboratory Services, Illumina	RCV001145723	SCV001306416	benign	Familial visceral amyloidosis, Ostertag type	2018-01-13	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003987750	SCV004803796	benign	not specified	2024-01-26	criteria provided, single submitter	clinical testing	Variant summary: FGA c.1366A>G (p.Thr456Ala) results in a non-conservative amino acid change located in the C domain (IPR021996) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0007 in 251250 control chromosomes, predominantly at a frequency of 0.0092 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The high frequency suggests that the variant is likely not associated with disease. To our knowledge, no occurrence of c.1366A>G in individuals affected with Dysfibrinogenemia, Congenital and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 783428). Based on the evidence outlined above, the variant was classified as benign.
Birmingham Platelet Group; University of Birmingham	RCV001270514	SCV001450813	uncertain significance	Abnormal bleeding; Thrombocytopenia	2020-05-01	no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV004535938	SCV004738018	benign	FGA-related disorder	2020-03-09	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).