Submissions for variant NM_000492.4(CFTR):c.2820T>G (p.Thr940=)

gnomAD frequency: 0.00148  dbSNP: rs60887846

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000217477	SCV000110857	likely benign	not specified	2016-12-15	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000217477	SCV000268870	benign	not specified	2013-02-21	criteria provided, single submitter	clinical testing	Thr940Thr in exon 17 of CFTR: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 0.5% (21/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs60887846).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000537570	SCV000625741	benign	Cystic fibrosis	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000217477	SCV000696926	likely benign	not specified	2019-01-28	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.2820T>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00044 in 277144 control chromosomes, predominantly at a frequency of 0.0045 within the African subpopulation in the gnomAD database. This frequency is somewhat lower than expected for a pathogenic variant in CFTR causing Cystic Fibrosis (0.0045 vs 0.013), nevertheless the variant still might represent a benign polymorphism. To our knowledge, no occurrence of c.2820T>G in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1 benign, 1 likely benign, 1 VUS). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587160	SCV000889299	likely benign	not provided	2023-01-30	criteria provided, single submitter	clinical testing
Core Molecular Diagnostic Lab, McGill University Health Centre	RCV000537570	SCV000914209	likely benign	Cystic fibrosis	2019-05-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587160	SCV001160029	benign	not provided	2023-03-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000537570	SCV001177675	benign	Cystic fibrosis	2015-06-22	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Sema4, Sema4	RCV002257404	SCV002529705	likely benign	Hereditary pancreatitis	2021-02-04	criteria provided, single submitter	curation
Johns Hopkins Genomics, Johns Hopkins University	RCV000537570	SCV002570383	likely benign	Cystic fibrosis	2022-07-23	criteria provided, single submitter	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000537570	SCV000692327	uncertain significance	Cystic fibrosis	2015-12-29	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000537570	SCV001455995	likely benign	Cystic fibrosis	2019-08-06	no assertion criteria provided	clinical testing