rs397508380
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000492.4(CFTR):c.2472del(p.Asn825ThrfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,390,544 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. I824I) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000492.4 frameshift
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.2472del | p.Asn825ThrfsTer5 | frameshift_variant | 14/27 | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.2472del | p.Asn825ThrfsTer5 | frameshift_variant | 14/27 | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000519 AC: 1AN: 192696Hom.: 0 AF XY: 0.00000970 AC XY: 1AN XY: 103096
GnomAD4 exome AF: 0.00000144 AC: 2AN: 1390544Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1AN XY: 687226
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cystic fibrosis Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2020 | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with cystic fibrosis (PMID: 7687986). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as CF2603/4delT in the literature. ClinVar contains an entry for this variant (Variation ID: 53494). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn825Thrfs*5) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). - |
not provided, no classification provided | literature only | ClinVar Staff, National Center for Biotechnology Information (NCBI) | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 14, 2020 | The c.2472delT pathogenic mutation, located in coding exon 14 of the CFTR gene, results from a deletion of one nucleotide at nucleotide position 2472, causing a translational frameshift with a predicted alternate stop codon (p.N825Tfs*5). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
CFTR-related disorders Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 17, 2017 | - - |
Cystic fibrosis;C0238339:Hereditary pancreatitis;C0403814:Congenital bilateral aplasia of vas deferens from CFTR mutation;C2749757:Bronchiectasis with or without elevated sweat chloride 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 09, 2022 | - - |
Bronchiectasis with or without elevated sweat chloride 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 26, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at