rs367752002

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000379802.8(DSP):ā€‹c.2684A>Cā€‹(p.Tyr895Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. Y895C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DSP
ENST00000379802.8 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.43
Variant links:
Genes affected
DSP (HGNC:3052): (desmoplakin) This gene encodes a protein that anchors intermediate filaments to desmosomal plaques and forms an obligate component of functional desmosomes. Mutations in this gene are the cause of several cardiomyopathies and keratodermas, including skin fragility-woolly hair syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14848101).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DSPNM_004415.4 linkuse as main transcriptc.2684A>C p.Tyr895Ser missense_variant 19/24 ENST00000379802.8 NP_004406.2
DSPNM_001319034.2 linkuse as main transcriptc.2684A>C p.Tyr895Ser missense_variant 19/24 NP_001305963.1
DSPNM_001008844.3 linkuse as main transcriptc.2684A>C p.Tyr895Ser missense_variant 19/24 NP_001008844.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DSPENST00000379802.8 linkuse as main transcriptc.2684A>C p.Tyr895Ser missense_variant 19/241 NM_004415.4 ENSP00000369129 P2P15924-1
DSPENST00000418664.2 linkuse as main transcriptc.2684A>C p.Tyr895Ser missense_variant 19/241 ENSP00000396591 A2P15924-2
DSPENST00000710359.1 linkuse as main transcriptc.2684A>C p.Tyr895Ser missense_variant 19/24 ENSP00000518230 A2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251304
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461814
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
21
DANN
Benign
0.94
DEOGEN2
Uncertain
0.73
D;.
Eigen
Benign
-0.11
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.24
N;N
MutationTaster
Benign
0.99
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.13
Sift
Benign
1.0
T;T
Sift4G
Benign
0.64
T;T
Polyphen
0.010
B;.
Vest4
0.81
MutPred
0.60
Gain of disorder (P = 0.0392);Gain of disorder (P = 0.0392);
MVP
0.50
MPC
0.46
ClinPred
0.40
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs367752002; hg19: chr6-7576580; API