chr11-108247118-CTG-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000051.4(ATM):βc.1058_1059delβ(p.Cys353SerfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. C353C) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000051.4 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 |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.1058_1059del | p.Cys353SerfsTer5 | frameshift_variant | 8/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.1058_1059del | p.Cys353SerfsTer5 | frameshift_variant | 8/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461448Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727020
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 02, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2022 | The c.1058_1059delGT pathogenic mutation, located in coding exon 7 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 1058 to 1059, causing a translational frameshift with a predicted alternate stop codon (p.C353Sfs*5). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. - |
Ataxia-telangiectasia syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 04, 2023 | ClinVar contains an entry for this variant (Variation ID: 490410). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with ATM-related cancers (PMID: 21933854, 29470806, 29506128). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys353Serfs*5) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2019 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek 2016); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Mannan 2016, Lowery 2018, Singh 2018); This variant is associated with the following publications: (PMID: 21933854, 29470806, 26911350, 29506128, 10023947) - |
Familial cancer of breast Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at