rs1554106489
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate
The NM_004415.4(DSP):c.780A>G(p.Lys260=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
DSP
NM_004415.4 splice_region, synonymous
NM_004415.4 splice_region, synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 6.95
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 6-7565361-A-G is Benign according to our data. Variant chr6-7565361-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 534324.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.780A>G | p.Lys260= | splice_region_variant, synonymous_variant | 7/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.780A>G | p.Lys260= | splice_region_variant, synonymous_variant | 7/24 | ||
DSP | NM_001008844.3 | c.780A>G | p.Lys260= | splice_region_variant, synonymous_variant | 7/24 | ||
DSP | NM_001406591.1 | c.780A>G | p.Lys260= | splice_region_variant, synonymous_variant | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.780A>G | p.Lys260= | splice_region_variant, synonymous_variant | 7/24 | 1 | NM_004415.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727212
GnomAD4 exome
AF:
AC:
1
AN:
1461824
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727212
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
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 submitter | clinical testing | Invitae | Dec 14, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at