rs63751246
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_000251.3(MSH2):c.82G>A(p.Glu28Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,599,874 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E28D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000251.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH2 | NM_000251.3 | c.82G>A | p.Glu28Lys | missense_variant | 1/16 | ENST00000233146.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH2 | ENST00000233146.7 | c.82G>A | p.Glu28Lys | missense_variant | 1/16 | 1 | NM_000251.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000456 AC: 1AN: 219386Hom.: 0 AF XY: 0.00000836 AC XY: 1AN XY: 119660
GnomAD4 exome AF: 6.91e-7 AC: 1AN: 1447606Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 718938
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74396
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 04, 2022 | The p.E28K variant (also known as c.82G>A), located in coding exon 1 of the MSH2 gene, results from a G to A substitution at nucleotide position 82. The glutamic acid at codon 28 is replaced by lysine, an amino acid with similar properties. This amino acid position is well 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. - |
Hereditary nonpolyposis colorectal neoplasms Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at