chr11-108330398-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000051.4(ATM):āc.7492T>Gā(p.Ser2498Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. S2498F) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.7492T>G | p.Ser2498Ala | missense_variant | 50/63 | ENST00000675843.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATM | ENST00000675843.1 | c.7492T>G | p.Ser2498Ala | missense_variant | 50/63 | NM_000051.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 02, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 11, 2020 | The p.S2498A variant (also known as c.7492T>G), located in coding exon 49 of the ATM gene, results from a T to G substitution at nucleotide position 7492. The serine at codon 2498 is replaced by alanine, an amino acid with similar properties. This alteration has been reported as a variant of uncertain significance in a male patient diagnosed with an MMR proficient sigmoid colon cancer at age 47 (Pearlman R et al. JAMA Oncol, 2017 Apr;3:464-471). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Ataxia-telangiectasia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2498 of the ATM protein (p.Ser2498Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ATM-related conditions (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 407695). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at