11-108331494-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000051.4(ATM):āc.7566A>Gā(p.Gln2522Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,376 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000051.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.7566A>G | p.Gln2522Gln | synonymous_variant | Exon 51 of 63 | ENST00000675843.1 | NP_000042.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152014Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251308Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135852
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461362Hom.: 1 Cov.: 31 AF XY: 0.0000289 AC XY: 21AN XY: 726976
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74256
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2Benign:1
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This synonymous variant does not change the amino acid sequence of the ATM protein, but it causes an A to G substitution in exon 51 of the ATM gene. Splice site prediction tools suggest that this variant may create a new splice acceptor site, although this prediction has not been confirmed in published RNA studies. This variant has been reported in individuals affected with breast cancer (PMID: 30093976, 30287823) and in unaffected individuals (PMID: 30287823). This variant has been identified in 6/251308 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Familial cancer of breast Uncertain:1Benign:1
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This variant is considered likely benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Ataxia-telangiectasia syndrome;C0346153:Familial cancer of breast Uncertain:1
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not provided Uncertain:1
In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Observed in individuals with breast cancer, but also in unaffected controls (Chan 2018, Momozawa 2018); This variant is associated with the following publications: (PMID: 29338689, 30287823, 30093976) -
not specified Benign:1
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Ataxia-telangiectasia syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at