rs1060501677
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000051.4(ATM):βc.3206delβ(p.Pro1069LeufsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. P1069P) 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.3206del | p.Pro1069LeufsTer2 | frameshift_variant | 22/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.3206del | p.Pro1069LeufsTer2 | frameshift_variant | 22/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461788Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727198
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2023 | This sequence change creates a premature translational stop signal (p.Pro1069Leufs*2) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 407680). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 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); This variant is associated with the following publications: (PMID: 30420857) - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2019 | - - |
Hereditary cancer-predisposing syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jun 01, 2021 | This variant deletes 1 nucleotide in exon 22 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 30, 2023 | The c.3206delC pathogenic mutation, located in coding exon 21 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 3206, causing a translational frameshift with a predicted alternate stop codon (p.P1069Lfs*2). 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. - |
Familial cancer of breast Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Jan 19, 2024 | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 24, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at