rs372598337
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001943.5(DSG2):c.1089G>A(p.Ser363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,614,050 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 1 hom. )
Consequence
DSG2
NM_001943.5 synonymous
NM_001943.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.277
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 18-31531061-G-A is Benign according to our data. Variant chr18-31531061-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 416112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.277 with no splicing effect.
BS2
?
High AC in GnomAd at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSG2 | NM_001943.5 | c.1089G>A | p.Ser363= | synonymous_variant | 9/15 | ENST00000261590.13 | |
DSG2 | XM_047437315.1 | c.555G>A | p.Ser185= | synonymous_variant | 10/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSG2 | ENST00000261590.13 | c.1089G>A | p.Ser363= | synonymous_variant | 9/15 | 1 | NM_001943.5 | P1 | |
DSG2 | ENST00000683614.2 | n.920G>A | non_coding_transcript_exon_variant | 7/7 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152126Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000521 AC: 13AN: 249392Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135302
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GnomAD4 exome AF: 0.000137 AC: 200AN: 1461806Hom.: 1 Cov.: 31 AF XY: 0.000131 AC XY: 95AN XY: 727208
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74442
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ClinVar
Significance: Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 14, 2018 | The p.Ser363Ser variant (rs372598337) does not alter the amino acid sequence of the DSG2 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with cardiomyopathy in medical literature or in gene specific variation databases. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.006 percent (identified on 16 out of 277,022 chromosomes) and has been reported to the ClinVar database as a likely benign variant (Variant ID: 416112). Based on these observations, the p.Ser363Ser variant is likely to be benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 09, 2021 | - - |
Arrhythmogenic right ventricular cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 07, 2023 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 08, 2018 | - - |
Arrhythmogenic right ventricular dysplasia 10 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2020 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at