chr7-117606701-A-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000492.4(CFTR):c.2936A>T(p.Asp979Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D979A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000492.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.2936A>T | p.Asp979Val | missense_variant | 18/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.2936A>T | p.Asp979Val | missense_variant | 18/27 | 1 | NM_000492.4 | P2 | |
ENST00000456270.1 | n.178-1712T>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 27
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Cystic fibrosis Pathogenic:2Other:1
not provided, no classification provided | literature only | ClinVar Staff, National Center for Biotechnology Information (NCBI) | - | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 27, 2021 | The p.D979V variant (also known as c.2936A>T), located in coding exon 18 of the CFTR gene, results from an A to T substitution at nucleotide position 2936. The aspartic acid at codon 979 is replaced by valine, an amino acid with highly dissimilar properties. This variant has been detected in cohorts of French and Russian patients with cystic fibrosis (Plouvier E et al. Ann. Genet., 1997;40:185-8; Claustres M et al. Hum Mutat, 2000;16:143-56; Petrova NV et al. Genes (Basel), 2020 05;11:). In one functional study, this alteration caused CFTR processing defects (Clain J et al. J. Biol. Chem., 2001 Mar;276:9045-9). In other studies, this variant significantly reduced CFTR function compared to wild type (Han ST et al. JCI Insight, 2018 07;3; Raraigh KS et al. Am J Hum Genet, 2018 06;102:1062-1077). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. - |
Pathogenic, reviewed by expert panel | research | CFTR2 | Dec 08, 2017 | - - |
Cystic fibrosis;na:CFTR-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | curation | CFTR-France | Jan 29, 2018 | the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at