rs777004957

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024422.6(DSC2):​c.2287G>T​(p.Ala763Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A763T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

DSC2
NM_024422.6 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.761
Variant links:
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04398349).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DSC2NM_024422.6 linkuse as main transcriptc.2287G>T p.Ala763Ser missense_variant 15/16 ENST00000280904.11 NP_077740.1
DSC2NM_004949.5 linkuse as main transcriptc.2287G>T p.Ala763Ser missense_variant 15/17 NP_004940.1
DSC2NM_001406506.1 linkuse as main transcriptc.1858G>T p.Ala620Ser missense_variant 15/16 NP_001393435.1
DSC2NM_001406507.1 linkuse as main transcriptc.1858G>T p.Ala620Ser missense_variant 15/17 NP_001393436.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DSC2ENST00000280904.11 linkuse as main transcriptc.2287G>T p.Ala763Ser missense_variant 15/161 NM_024422.6 ENSP00000280904 P1Q02487-1
DSC2ENST00000251081.8 linkuse as main transcriptc.2287G>T p.Ala763Ser missense_variant 15/171 ENSP00000251081 Q02487-2
DSC2ENST00000648081.1 linkuse as main transcriptc.1858G>T p.Ala620Ser missense_variant 16/17 ENSP00000497441
DSC2ENST00000682357.1 linkuse as main transcriptc.1858G>T p.Ala620Ser missense_variant 15/16 ENSP00000507826

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.098
DANN
Benign
0.71
DEOGEN2
Benign
0.038
T;.;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.31
T;T;T
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.044
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.075
N;N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
0.21
N;N;.
REVEL
Benign
0.012
Sift
Benign
0.76
T;T;.
Sift4G
Benign
0.73
T;T;.
Polyphen
0.0060
B;B;.
Vest4
0.066
MutPred
0.36
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;
MVP
0.29
MPC
0.070
ClinPred
0.029
T
GERP RS
-2.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.033
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777004957; hg19: chr18-28649081; API