rs8095704
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000261590.13(DSG2):āc.3135A>Cā(p.Thr1045=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,614,218 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0073 ( 19 hom., cov: 32)
Exomes š: 0.00069 ( 10 hom. )
Consequence
DSG2
ENST00000261590.13 synonymous
ENST00000261590.13 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.292
Genes affected
DSG2 (HGNC:3049): (desmoglein 2) This gene encodes a member of the desmoglein family and cadherin cell adhesion molecule superfamily of proteins. Desmogleins are calcium-binding transmembrane glycoprotein components of desmosomes, cell-cell junctions between epithelial, myocardial, and other cell types. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This gene is present in a gene cluster with other desmoglein gene family members on chromosome 18. Mutations in this gene have been associated with arrhythmogenic right ventricular dysplasia, familial, 10. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 18-31546521-A-C is Benign according to our data. Variant chr18-31546521-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 36013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31546521-A-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.292 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00733 (1116/152328) while in subpopulation AFR AF= 0.0242 (1007/41576). AF 95% confidence interval is 0.023. There are 19 homozygotes in gnomad4. There are 482 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1116 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSG2 | NM_001943.5 | c.3135A>C | p.Thr1045= | synonymous_variant | 15/15 | ENST00000261590.13 | NP_001934.2 | |
DSG2-AS1 | NR_045216.1 | n.1346-615T>G | intron_variant, non_coding_transcript_variant | |||||
DSG2 | XM_047437315.1 | c.2601A>C | p.Thr867= | synonymous_variant | 16/16 | XP_047293271.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSG2 | ENST00000261590.13 | c.3135A>C | p.Thr1045= | synonymous_variant | 15/15 | 1 | NM_001943.5 | ENSP00000261590 | P1 | |
DSG2-AS1 | ENST00000583706.5 | n.1384-615T>G | intron_variant, non_coding_transcript_variant | 5 | ||||||
DSG2-AS1 | ENST00000657343.1 | n.697-615T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00733 AC: 1116AN: 152210Hom.: 19 Cov.: 32
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GnomAD3 exomes AF: 0.00169 AC: 421AN: 249456Hom.: 6 AF XY: 0.00106 AC XY: 144AN XY: 135330
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GnomAD4 exome AF: 0.000691 AC: 1010AN: 1461890Hom.: 10 Cov.: 32 AF XY: 0.000558 AC XY: 406AN XY: 727244
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GnomAD4 genome AF: 0.00733 AC: 1116AN: 152328Hom.: 19 Cov.: 32 AF XY: 0.00647 AC XY: 482AN XY: 74492
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 22, 2013 | Thr1045Thr in exon 15 of DSG2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, and is not located wi thin the splice consensus sequence and has been identified in 2.3% (92/4044) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs8095704). - |
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 | Clinical Genetics, Academic Medical Center | - | - - |
Cardiomyopathy Benign:3
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 17, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Dec 31, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Cohesion Phenomics | Sep 23, 2022 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 13, 2021 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Arrhythmogenic right ventricular dysplasia 10 Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
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 | - - |
Cardiac arrhythmia Benign:1
Benign, no assertion criteria provided | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 13, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at