11-108329151-C-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000051.4(ATM):c.7220C>A(p.Ser2407Ter) variant causes a stop gained 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S2407S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000051.4 stop_gained
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.7220C>A | p.Ser2407Ter | stop_gained | 49/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.7220C>A | p.Ser2407Ter | stop_gained | 49/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 01, 2021 | The p.S2407* pathogenic mutation (also known as c.7220C>A), located in coding exon 48 of the ATM gene, results from a C to A substitution at nucleotide position 7220. This changes the amino acid from a serine to a stop codon within coding exon 48. 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. - |
Pathogenic, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 07, 2021 | This variant changes 1 nucleotide in exon 49 of the ATM gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with breast and colorectal cancer (PMID: 32792570). 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. - |
Familial cancer of breast Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Jan 31, 2024 | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 11, 2023 | - - |
Ataxia-telangiectasia syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 05, 2023 | This sequence change creates a premature translational stop signal (p.Ser2407*) 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). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 524287). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 32427313). This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at