rs781667894
Variant names:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_024422.6(DSC2):c.750T>C(p.Phe250Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,124 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
DSC2
NM_024422.6 synonymous
NM_024422.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.613
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 -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 18-31087694-A-G is Benign according to our data. Variant chr18-31087694-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 416271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-31087694-A-G is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.613 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00000753 (11/1460878) while in subpopulation EAS AF= 0.000277 (11/39650). AF 95% confidence interval is 0.000155. There are 0 homozygotes in gnomad4_exome. There are 3 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DSC2 | NM_024422.6 | c.750T>C | p.Phe250Phe | synonymous_variant | Exon 6 of 16 | ENST00000280904.11 | NP_077740.1 | |
| DSC2 | NM_004949.5 | c.750T>C | p.Phe250Phe | synonymous_variant | Exon 6 of 17 | NP_004940.1 | ||
| DSC2 | NM_001406506.1 | c.321T>C | p.Phe107Phe | synonymous_variant | Exon 6 of 16 | NP_001393435.1 | ||
| DSC2 | NM_001406507.1 | c.321T>C | p.Phe107Phe | synonymous_variant | Exon 6 of 17 | NP_001393436.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DSC2 | ENST00000280904.11 | c.750T>C | p.Phe250Phe | synonymous_variant | Exon 6 of 16 | 1 | NM_024422.6 | ENSP00000280904.6 | ||
| DSC2 | ENST00000251081.8 | c.750T>C | p.Phe250Phe | synonymous_variant | Exon 6 of 17 | 1 | ENSP00000251081.6 | |||
| DSC2 | ENST00000648081.1 | c.321T>C | p.Phe107Phe | synonymous_variant | Exon 7 of 17 | ENSP00000497441.1 | ||||
| DSC2 | ENST00000682357.1 | c.321T>C | p.Phe107Phe | synonymous_variant | Exon 6 of 16 | ENSP00000507826.1 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250816Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135624
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460878Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726778
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GnomAD4 genome 0.0000131 AC: 2AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74378
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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
Oct 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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