rs1060501580
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000051.4(ATM):βc.5681_5682delβ(p.Glu1894AlafsTer9) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,460,748 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. S1893S) has been classified as 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.5681_5682del | p.Glu1894AlafsTer9 | frameshift_variant | 38/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.5681_5682del | p.Glu1894AlafsTer9 | frameshift_variant | 38/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460748Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 726722
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2023 | This sequence change creates a premature translational stop signal (p.Glu1894Alafs*9) 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: 407525). For these reasons, this variant has been classified as Pathogenic. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 09, 2020 | The c.5681_5682delAG pathogenic mutation, located in coding exon 37 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 5681 to 5682, causing a translational frameshift with a predicted alternate stop codon (p.E1894Afs*9). This alteration was identified in a patient with ataxia-telangiectasia in conjunction with another ATM mutation, c.748C>T (p.R250*) (Jackson TJ et al. Dev Med Child Neurol. 2016 07;58:690-7). In addition to the clinical data presented in the literature, 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:1
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Jan 25, 2024 | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at