rs532718510
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_024422.6(DSC2):c.*1927T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 152,304 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 Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DSC2
NM_024422.6 3_prime_UTR
NM_024422.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.25
Publications
0 publications found
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]
DSC2 Gene-Disease associations (from GenCC):
- familial isolated arrhythmogenic right ventricular dysplasiaInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- arrhythmogenic right ventricular dysplasia 11Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- colorectal adenomaInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000269 (41/152304) while in subpopulation SAS AF = 0.000415 (2/4822). AF 95% confidence interval is 0.000218. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| DSC2 | NM_024422.6 | c.*1927T>C | 3_prime_UTR_variant | Exon 16 of 16 | ENST00000280904.11 | NP_077740.1 | ||
| DSC2 | NM_004949.5 | c.*2135T>C | 3_prime_UTR_variant | Exon 17 of 17 | NP_004940.1 | |||
| DSC2 | NM_001406506.1 | c.*1927T>C | 3_prime_UTR_variant | Exon 16 of 16 | NP_001393435.1 | |||
| DSC2 | NM_001406507.1 | c.*2135T>C | 3_prime_UTR_variant | Exon 17 of 17 | NP_001393436.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.000269 AC: 41AN: 152186Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
41
AN:
152186
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 10Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 6
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
10
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
6
African (AFR)
AF:
AC:
0
AN:
2
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AC:
0
AN:
0
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
AC:
0
AN:
6
Other (OTH)
AF:
AC:
0
AN:
2
GnomAD4 genome 0.000269 AC: 41AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74472 show subpopulations
GnomAD4 genome
AF:
AC:
41
AN:
152304
Hom.:
Cov.:
32
AF XY:
AC XY:
17
AN XY:
74472
show subpopulations
African (AFR)
AF:
AC:
2
AN:
41574
American (AMR)
AF:
AC:
2
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
AC:
8
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
2
AN:
4822
European-Finnish (FIN)
AF:
AC:
0
AN:
10628
Middle Eastern (MID)
AF:
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
AC:
22
AN:
68024
Other (OTH)
AF:
AC:
2
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 11 Uncertain:1
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
not provided Uncertain:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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