ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1210-2A>C (rs397508179)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001372 SCV001158570 pathogenic not specified 2019-06-26 criteria provided, single submitter clinical testing The CFTR c.1210-2A>C variant (rs397508179), also known as 1342-2A>C for traditional nomenclature, is described in the literature in two siblings affected with CF who were homozygous for the variant, and in another affected individual who carried a nonsense variant on the opposite allele (Dork 1993). The c.1210-2A>C variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant disrupts the canonical splice acceptor site, which is likely to negatively impact gene function. Based on available information, this variant is considered to be pathogenic. REFERENCES Dork T et al. Severe splice site mutation preceding exon 9 of the CFTR gene. Hum Mol Genet. 1993 Aug;2(8):1313-4.
Baylor Genetics RCV001004258 SCV001163134 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001193108 SCV001361721 pathogenic Cystic fibrosis 2019-01-17 criteria provided, single submitter clinical testing Variant summary: CFTR c.1210-2A>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. This variant was detected in two Cystic Fibrosis families from Southwest Germany. In the first family, the homozygous twins were 15 months old and pancreas insufficient. In the second family, the affected girl is a compound heterozygote for c.1210-2A>C (legacy name 1342-2 A->C) and Y1092X. She was 13 years old, pancreas insufficient and colonized with P aeruginosa (Sickkids database). The variant was absent in 242414 control chromosomes. A peer-reviewed publication reporting the findings presented in the Sickkids database was not immediately available at the time of this classification. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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