rs1042769
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001943.5(DSG2):āc.2505A>Gā(p.Thr835=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,976 control chromosomes in the GnomAD database, including 13,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. T835T) has been classified as Likely benign.
Frequency
Consequence
NM_001943.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSG2 | NM_001943.5 | c.2505A>G | p.Thr835= | synonymous_variant | 15/15 | ENST00000261590.13 | |
DSG2-AS1 | NR_045216.1 | n.1361T>C | non_coding_transcript_exon_variant | 4/6 | |||
DSG2 | XM_047437315.1 | c.1971A>G | p.Thr657= | synonymous_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSG2 | ENST00000261590.13 | c.2505A>G | p.Thr835= | synonymous_variant | 15/15 | 1 | NM_001943.5 | P1 | |
DSG2-AS1 | ENST00000583706.5 | n.1399T>C | non_coding_transcript_exon_variant | 4/6 | 5 | ||||
DSG2-AS1 | ENST00000657343.1 | n.712T>C | non_coding_transcript_exon_variant | 4/4 |
Frequencies
GnomAD3 genomes ? AF: 0.177 AC: 26974AN: 151986Hom.: 3236 Cov.: 32
GnomAD3 exomes AF: 0.125 AC: 31107AN: 249234Hom.: 2543 AF XY: 0.120 AC XY: 16174AN XY: 135236
GnomAD4 exome AF: 0.110 AC: 160751AN: 1461874Hom.: 10258 Cov.: 32 AF XY: 0.108 AC XY: 78724AN XY: 727242
GnomAD4 genome ? AF: 0.178 AC: 27023AN: 152102Hom.: 3247 Cov.: 32 AF XY: 0.174 AC XY: 12923AN XY: 74358
ClinVar
Submissions by phenotype
not specified Benign:8
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 06, 2007 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 20, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Cardiomyopathy Benign:2
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 08, 2018 | - - |
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
Arrhythmogenic right ventricular dysplasia 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 09, 2015 | This alteration is classified as 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at