chr6-7574719-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_004415.4(DSP):āc.2360A>Gā(p.Tyr787Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000638 in 1,614,062 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y787S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.2360A>G | p.Tyr787Cys | missense_variant | 17/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.2360A>G | p.Tyr787Cys | missense_variant | 17/24 | ||
DSP | NM_001008844.3 | c.2360A>G | p.Tyr787Cys | missense_variant | 17/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.2360A>G | p.Tyr787Cys | missense_variant | 17/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.2360A>G | p.Tyr787Cys | missense_variant | 17/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.2360A>G | p.Tyr787Cys | missense_variant | 17/24 | A2 | |||
DSP | ENST00000684395.1 | n.1001A>G | non_coding_transcript_exon_variant | 4/5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251398Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135870
GnomAD4 exome AF: 0.0000657 AC: 96AN: 1461872Hom.: 1 Cov.: 32 AF XY: 0.0000674 AC XY: 49AN XY: 727234
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74364
ClinVar
Submissions by phenotype
Lethal acantholytic epidermolysis bullosa Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Woolly hair-skin fragility syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Arrhythmogenic right ventricular dysplasia 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 05, 2022 | Variant summary: DSP c.2360A>G (p.Tyr787Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251398 control chromosomes, predominantly at a frequency of 0.0015 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 8 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (0.0002), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.2360A>G has been reported in the literature in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. These reports do not provide unequivocal conclusions about association of the variant with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign n=2, VUS n=1). Based on the evidence outlined above, the variant was classified as likely benign. - |
Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 15, 2023 | - - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2023 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 14, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at