rs397516928
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_004415.4(DSP):c.2866A>T(p.Asn956Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,611,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N956S) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSP | NM_004415.4 | c.2866A>T | p.Asn956Tyr | missense_variant | 20/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.2866A>T | p.Asn956Tyr | missense_variant | 20/24 | ||
DSP | NM_001008844.3 | c.2866A>T | p.Asn956Tyr | missense_variant | 20/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.2866A>T | p.Asn956Tyr | missense_variant | 20/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.2866A>T | p.Asn956Tyr | missense_variant | 20/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.2866A>T | p.Asn956Tyr | missense_variant | 20/24 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152234Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000101 AC: 25AN: 248532Hom.: 0 AF XY: 0.000127 AC XY: 17AN XY: 134200
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1458808Hom.: 0 Cov.: 30 AF XY: 0.0000276 AC XY: 20AN XY: 725416
GnomAD4 genome ? AF: 0.0000656 AC: 10AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74504
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 20, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Asn956Tyr varia nt (DSP) has been identifed in 2/1054 reportedly healthy control chromosomes (Ka pplinger 2011, Wei_2011). Computational analyses (biochemical amino acid propert ies, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that this variant may not impact the protein, though this information is not predictive enough to rul e out pathogenicity. Although this data suggests that the Asn956Tyr variant may be benign, additional information is needed to fully assess its clinical signifi cance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35628349, 22216297, 21636032, 24503780) - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 07, 2021 | The c.2866A>T (p.N956Y) alteration is located in exon 20 (coding exon 20) of the DSP gene. This alteration results from a A to T substitution at nucleotide position 2866, causing the asparagine (N) at amino acid position 956 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
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 08, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 30, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at