ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.2936A>C (p.Asp979Ala) (rs397508462)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000586469 SCV000696934 likely pathogenic Congenital bilateral absence of the vas deferens 2019-01-07 criteria provided, single submitter clinical testing Variant summary: CFTR c.2936A>C (p.Asp979Ala) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 246182 control chromosomes (gnomAD and publications). The variant, c.2936A>C, had been detected in at least two Congenital Bilateral Absence of the Vas Deferens (CBAVD) patients with another pathogenic variant (5T allele) in trans (Dork_1997, Mak_1999). The variant was also detected, and assumed to have a worsening effect, in two siblings with severe CF, together with a CF-causing mutation (p.R347H) in cis that was inherited from a healthy mother and p.F508del in the other allele inherited from a healthy father (Hojo_1998). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The variant was shown to have a mild residual activity in isolation, which is consistent with the mild CFTR-related phenotype that has been observed (i.e. CBAVD (Clain_2001)). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Counsyl RCV000577756 SCV000800040 uncertain significance Cystic fibrosis 2018-05-18 criteria provided, single submitter clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577756 SCV000679363 not provided Cystic fibrosis no assertion provided literature only

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