chr11-94447278-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_005591.4(MRE11):c.1724G>A(p.Gly575Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G575V) has been classified as Uncertain significance.
Frequency
Consequence
NM_005591.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRE11 | NM_005591.4 | c.1724G>A | p.Gly575Asp | missense_variant | 15/20 | ENST00000323929.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRE11 | ENST00000323929.8 | c.1724G>A | p.Gly575Asp | missense_variant | 15/20 | 1 | NM_005591.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251388Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135866
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461802Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727210
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74344
ClinVar
Submissions by phenotype
Ataxia-telangiectasia-like disorder 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 03, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2023 | The p.G575D variant (also known as c.1724G>A), located in coding exon 14 of the MRE11A gene, results from a G to A substitution at nucleotide position 1724. The glycine at codon 575 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been reported in individuals with a personal history of ovarian and colon cancer from a cohort of 1191 cancer index patients who underwent clinical evaluation and testing with multigene panels (Chan GHJ et al. Oncotarget, 2018 Jul;9:30649-30660). This amino acid position is highly conserved 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. - |
Ataxia-telangiectasia-like disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 575 of the MRE11 protein (p.Gly575Asp). This variant is present in population databases (rs376555330, gnomAD 0.08%). This missense change has been observed in individual(s) with colon cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 220769). 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: "Tolerated"; 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at