Submissions for variant NM_000492.4(CFTR):c.627A>G (p.Ala209=)

gnomAD frequency: 0.00002  dbSNP: rs397508773

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001165379	SCV001327568	uncertain significance	CFTR-related disorder	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000577039	SCV001689502	likely benign	Cystic fibrosis	2024-01-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000577039	SCV001822015	likely benign	Cystic fibrosis	2021-07-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001588878	SCV001822016	uncertain significance	Congenital bilateral aplasia of vas deferens from CFTR mutation	2021-07-22	criteria provided, single submitter	clinical testing
Mendelics	RCV002247440	SCV002518075	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000577039	SCV002660084	likely benign	Cystic fibrosis	2015-11-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002247440	SCV003922696	likely benign	not specified	2023-03-28	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577039	SCV000679173	not provided	Cystic fibrosis		no assertion provided	literature only
Servicio Canario de Salud, Hospital Universitario Nuestra Sra. de Candelaria	RCV000577039	SCV004041595	likely risk allele	Cystic fibrosis	2023-05-26	no assertion criteria provided	clinical testing	The c.627A>G p.(Ala209=) CFTR sinonimous variant has been reported in our laboratory, in compound heterocigous state, in 3 patients with clinical diagnosis of Cystic Fibrosis and elevated chloride in sweat. This allele is in linkage disequilibrium with the deep intronic variant c.2989-313A>T (Clinvar pathogenic variant Id 818113). This variant is present in population databases (gnomAD allele frequency 0.00001061). ClinVar contains an entry for this variant (Variation ID: 54031). In summary, if the synonymous variant c.627A>G p.(Ala209=) CFTR is identified, the pathogenic variant c.2989-313A>T located in intron 18 should be studied.