2-47800401-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_000179.3(MSH6):c.2418C>T(p.Ser806=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,826 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). Synonymous variant affecting the same amino acid position (i.e. S806S) has been classified as Likely benign.
Frequency
Consequence
NM_000179.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH6 | NM_000179.3 | c.2418C>T | p.Ser806= | synonymous_variant | 4/10 | ENST00000234420.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH6 | ENST00000234420.11 | c.2418C>T | p.Ser806= | synonymous_variant | 4/10 | 1 | NM_000179.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152000Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250478Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135378
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461826Hom.: 1 Cov.: 34 AF XY: 0.0000234 AC XY: 17AN XY: 727224
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152000Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74216
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 27, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016) - |
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The MSH6 p.Ser806= variant was not identified in the literature nor was it identified in the COGR, UMD-LSDB, Zhejiang University Database, Mismatch Repair Genes Variant Database, and or Insight Hereditary Tumors database. The variant was identified in dbSNP (ID: rs770992427) as "With other allele"), ClinVar (classified as likely benign by Ambry Genetics, Invitae, and GeneDx and as uncertain significance by two clinical laboratories: EGL Genetic Diagnostics and Integrated Genetics/Laboratory Corporation of America), and in Cosmic (1x in Haematopoietic and lymphoid tissue). The variant was identified in control databases in 5 of 276156 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 4 of 125786 chromosomes (freq: 0.00003), and East Asian in 1 of 18860 chromosomes (freq: 0.00005); it was not observed in the African, Other, Latino, Ashkenazi Jewish, Finnish, and or South Asian populations. The p.Ser806= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, the c.2418C nucleotide is weakly conserved and 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 07, 2014 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 29, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 22, 2014 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 27, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 03, 2019 | - - |
Lynch syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Hereditary nonpolyposis colorectal neoplasms Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at