rs397516959
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_004415.4(DSP):āc.7826T>Cā(p.Phe2609Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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.7826T>C | p.Phe2609Ser | missense_variant | 24/24 | ENST00000379802.8 | |
DSP | NM_001319034.2 | c.6497T>C | p.Phe2166Ser | missense_variant | 24/24 | ||
DSP | NM_001008844.3 | c.6029T>C | p.Phe2010Ser | missense_variant | 24/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSP | ENST00000379802.8 | c.7826T>C | p.Phe2609Ser | missense_variant | 24/24 | 1 | NM_004415.4 | P2 | |
DSP | ENST00000418664.2 | c.6029T>C | p.Phe2010Ser | missense_variant | 24/24 | 1 | A2 | ||
DSP | ENST00000710359.1 | c.6497T>C | p.Phe2166Ser | missense_variant | 24/24 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251292Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461878Hom.: 0 Cov.: 36 AF XY: 0.00000688 AC XY: 5AN XY: 727240
GnomAD4 genome ? Cov.: 32
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 | Mar 02, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Phe2609Ser vari ant (DSP) has not been reported in the literature nor previously identified by o ur laboratory. Phenylalanine (Phe) at position 2609 is not conserved in mammals (several other species carry a leucine), which suggests that a change at this p osition may not impact the protein. Additional computational analyses (biochemic al amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Collectively, this information is not predictive enough to rule out pathogenicity. Although the lack of amino a cid conservation at this position suggests that the Phe2609Ser variant may be be nign, additional information is needed to fully assess its clinical significance . - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 08, 2022 | This missense variant replaces phenylalanine with serine at codon 2609 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/282696 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Arrhythmogenic right ventricular dysplasia 8;C1854063:Arrhythmogenic cardiomyopathy with wooly hair and keratoderma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at