rs751447598

Positions:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000379802.8(DSP):​c.5698G>A​(p.Glu1900Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1900G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DSP
ENST00000379802.8 missense

Scores

3
11
5

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.63
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6
Variant 6-7582960-G-A is Benign according to our data. Variant chr6-7582960-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 578857.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DSPNM_004415.4 linkuse as main transcriptc.5698G>A p.Glu1900Lys missense_variant 24/24 ENST00000379802.8 NP_004406.2
DSPNM_001319034.2 linkuse as main transcriptc.4369G>A p.Glu1457Lys missense_variant 24/24 NP_001305963.1
DSPNM_001008844.3 linkuse as main transcriptc.3901G>A p.Glu1301Lys missense_variant 24/24 NP_001008844.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DSPENST00000379802.8 linkuse as main transcriptc.5698G>A p.Glu1900Lys missense_variant 24/241 NM_004415.4 ENSP00000369129 P2P15924-1
DSPENST00000418664.2 linkuse as main transcriptc.3901G>A p.Glu1301Lys missense_variant 24/241 ENSP00000396591 A2P15924-2
DSPENST00000710359.1 linkuse as main transcriptc.4369G>A p.Glu1457Lys missense_variant 24/24 ENSP00000518230 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251150
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135760
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461850
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.35
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.051
D
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.7
N;N
REVEL
Uncertain
0.36
Sift
Uncertain
0.0070
D;T
Sift4G
Uncertain
0.016
D;D
Polyphen
1.0
D;.
Vest4
0.82
MutPred
0.19
Gain of MoRF binding (P = 0.0579);.;
MVP
0.88
MPC
0.87
ClinPred
0.54
D
GERP RS
5.4
Varity_R
0.25
gMVP
0.46

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: rs751447598; hg19: chr6-7583193; COSMIC: COSV101131561; API