11-108343231-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PP3
The NM_000051.4(ATM):āc.8278C>Gā(p.Leu2760Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L2760F) has been classified as Uncertain significance.
Frequency
Consequence
NM_000051.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.8278C>G | p.Leu2760Val | missense_variant | 57/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.8278C>G | p.Leu2760Val | missense_variant | 57/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251380Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135864
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461684Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727142
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74308
ClinVar
Submissions by phenotype
Ataxia-telangiectasia syndrome Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 25, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 26, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2760 of the ATM protein (p.Leu2760Val). This variant is present in population databases (rs758609900, gnomAD 0.0009%). 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: 230632). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2023 | The p.L2760V variant (also known as c.8278C>G), located in coding exon 56 of the ATM gene, results from a C to G substitution at nucleotide position 8278. The leucine at codon 2760 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved through mammals in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 06, 2023 | This missense variant replaces leucine with valine at codon 2760 of the ATM protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has been identified in 1/251380 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at