rs562015789
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004415.4(DSP):c.5593A>T(p.Asn1865Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000219 in 1,614,142 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. N1865S) has been classified as Likely benign.
Frequency
Consequence
NM_004415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.5593A>T | p.Asn1865Tyr | missense_variant | 24/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.4264A>T | p.Asn1422Tyr | missense_variant | 24/24 | ||
DSP | NM_001008844.3 | c.3796A>T | p.Asn1266Tyr | missense_variant | 24/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.5593A>T | p.Asn1865Tyr | missense_variant | 24/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.3796A>T | p.Asn1266Tyr | missense_variant | 24/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.4264A>T | p.Asn1422Tyr | missense_variant | 24/24 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000441 AC: 111AN: 251478Hom.: 1 AF XY: 0.000603 AC XY: 82AN XY: 135914
GnomAD4 exome AF: 0.000228 AC: 334AN: 1461892Hom.: 1 Cov.: 32 AF XY: 0.000326 AC XY: 237AN XY: 727246
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74446
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 20, 2018 | The p.Asn1865Tyr variant (rs562015789) was reported in one individual from a healthy cohort of 427 subjects of various ethnic backgrounds (Kapplinger 211). This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.3 percent in the South Asian population (identified on 99 out of 30,782 chromosomes, including 1 homozygote), and has been reported to the ClinVar database (Variation ID: 357959). The asparagine at position 1865 is moderately conserved considering 12 species (Alamut v2.11) and computational analyses of the p.Asn1865Tyr variant on protein structure and function indicates a deleterious effect (SIFT: damaging, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Asn1865Tyr variant with certainty. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 08, 2020 | This variant is associated with the following publications: (PMID: 21636032) - |
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 | Dec 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 | Jan 01, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Oct 10, 2018 | - - |
Lethal acantholytic epidermolysis bullosa Benign:1
Likely benign, 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Woolly hair-skin fragility syndrome Benign:1
Likely benign, 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Arrhythmogenic right ventricular dysplasia 8 Benign:1
Likely benign, 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
DSP-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at