18-31066411-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_024422.6(DSC2):c.*1604A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 152,278 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.010 ( 27 hom., cov: 32)
Failed GnomAD Quality Control
Consequence
DSC2
NM_024422.6 3_prime_UTR
NM_024422.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.563
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 18-31066411-T-C is Benign according to our data. Variant chr18-31066411-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 326362.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1596/152278) while in subpopulation AFR AF= 0.0362 (1506/41568). AF 95% confidence interval is 0.0347. There are 27 homozygotes in gnomad4. There are 755 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 26 SD gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.*1604A>G | 3_prime_UTR_variant | 16/16 | ENST00000280904.11 | ||
DSC2 | NM_001406506.1 | c.*1604A>G | 3_prime_UTR_variant | 16/16 | |||
DSC2 | NM_001406507.1 | c.*1812A>G | 3_prime_UTR_variant | 17/17 | |||
DSC2 | NM_004949.5 | c.*1812A>G | 3_prime_UTR_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.*1604A>G | 3_prime_UTR_variant | 16/16 | 1 | NM_024422.6 | P1 | ||
DSC2 | ENST00000251081.8 | c.*1812A>G | 3_prime_UTR_variant | 17/17 | 1 | ||||
DSC2 | ENST00000648081.1 | c.*1604A>G | 3_prime_UTR_variant | 17/17 | |||||
DSC2 | ENST00000682357.1 | c.*1604A>G | 3_prime_UTR_variant | 16/16 |
Frequencies
GnomAD3 genomes ? AF: 0.0104 AC: 1589AN: 152160Hom.: 26 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0AC: 0AN: 0Hom.: 0 Cov.: 0AC XY: 0AN XY: 0
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GnomAD4 genome ? AF: 0.0105 AC: 1596AN: 152278Hom.: 27 Cov.: 32 AF XY: 0.0101 AC XY: 755AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Computational scores
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Name
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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