Submissions for variant NM_000492.4(CFTR):c.149C>A (p.Ser50Tyr)

gnomAD frequency: 0.00001  dbSNP: rs397508220

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000577356	SCV000788786	uncertain significance	Cystic fibrosis	2017-01-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194310	SCV001363738	uncertain significance	not specified	2024-03-14	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.149C>A (p.Ser50Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250440 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.149C>A has been reported in the literature in the compound heterozygous state with p.F508del in an individual affected with Congenital Bilateral Absence Of The Vas Deferens (Zielenski_1997). These data do not allow any conclusion about variant significance. 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: 9067761). ClinVar contains an entry for this variant (Variation ID: 53269). Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab	RCV000577356	SCV002027331	uncertain significance	Cystic fibrosis	2021-09-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000577356	SCV002700533	uncertain significance	Cystic fibrosis	2024-03-08	criteria provided, single submitter	clinical testing	The p.S50Y variant (also known as c.149C>A), located in coding exon 2 of the CFTR gene, results from a C to A substitution at nucleotide position 149. The serine at codon 50 is replaced by tyrosine, an amino acid with dissimilar properties. This alteration was described in an individual with congenital bilateral absence of the vas deferens (CBAVD), who was reported to also carry deltaF508 in trans (Zielenski J et al. Hum. Mutat., 1997;9:183-4). Of note, this alteration is also designated as 281C>A in published literature. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002490610	SCV002777877	likely pathogenic	Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation	2024-06-20	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577356	SCV000678899	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV001831729	SCV002080074	uncertain significance	CFTR-related disorder	2019-03-27	no assertion criteria provided	clinical testing