rs541223771
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_024422.6(DSC2):c.525T>C(p.Gly175Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
DSC2
NM_024422.6 synonymous
NM_024422.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.92
Genes affected
DSC2 (HGNC:3036): (desmocollin 2) This gene encodes a member of the desmocollin protein subfamily. Desmocollins, along with desmogleins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmocollin family members on chromosome 18. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia-11, and reduced protein expression has been described in several types of cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 18-31089544-A-G is Benign according to our data. Variant chr18-31089544-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 536282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.92 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.525T>C | p.Gly175Gly | synonymous_variant | Exon 5 of 16 | ENST00000280904.11 | NP_077740.1 | |
DSC2 | NM_004949.5 | c.525T>C | p.Gly175Gly | synonymous_variant | Exon 5 of 17 | NP_004940.1 | ||
DSC2 | NM_001406506.1 | c.96T>C | p.Gly32Gly | synonymous_variant | Exon 5 of 16 | NP_001393435.1 | ||
DSC2 | NM_001406507.1 | c.96T>C | p.Gly32Gly | synonymous_variant | Exon 5 of 17 | NP_001393436.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.525T>C | p.Gly175Gly | synonymous_variant | Exon 5 of 16 | 1 | NM_024422.6 | ENSP00000280904.6 | ||
DSC2 | ENST00000251081.8 | c.525T>C | p.Gly175Gly | synonymous_variant | Exon 5 of 17 | 1 | ENSP00000251081.6 | |||
DSC2 | ENST00000648081.1 | c.96T>C | p.Gly32Gly | synonymous_variant | Exon 6 of 17 | ENSP00000497441.1 | ||||
DSC2 | ENST00000682357.1 | c.96T>C | p.Gly32Gly | synonymous_variant | Exon 5 of 16 | ENSP00000507826.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461712Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727168
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1461712
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AN XY:
727168
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 11 Benign:1
Dec 11, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Cardiomyopathy Benign:1
Sep 17, 2018
Color Diagnostics, LLC DBA Color Health
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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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