chr18-31545954-A-C
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_001943.5(DSG2):āc.2568A>Cā(p.Lys856Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.000092 ( 0 hom., cov: 32)
Exomes š: 0.0028 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DSG2
NM_001943.5 missense
NM_001943.5 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 0.775
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0040987134).
BP6
Variant 18-31545954-A-C is Benign according to our data. Variant chr18-31545954-A-C is described in ClinVar as [Benign]. Clinvar id is 192185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSG2 | NM_001943.5 | c.2568A>C | p.Lys856Asn | missense_variant | 15/15 | ENST00000261590.13 | |
DSG2-AS1 | NR_045216.1 | n.1346-48T>G | intron_variant, non_coding_transcript_variant | ||||
DSG2 | XM_047437315.1 | c.2034A>C | p.Lys678Asn | missense_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSG2 | ENST00000261590.13 | c.2568A>C | p.Lys856Asn | missense_variant | 15/15 | 1 | NM_001943.5 | P1 | |
DSG2-AS1 | ENST00000583706.5 | n.1384-48T>G | intron_variant, non_coding_transcript_variant | 5 | |||||
DSG2-AS1 | ENST00000657343.1 | n.697-48T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 13AN: 151966Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00279 AC: 4071AN: 1457766Hom.: 0 Cov.: 32 AF XY: 0.00289 AC XY: 2097AN XY: 725122
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000921 AC: 14AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74342
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Aug 18, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of methylation at K856 (P = 6e-04);
MPC
ClinPred
T
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gMVP
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