rs397517397
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_024422.6(DSC2):c.2082G>T(p.Lys694Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,956 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 Uncertain significance (★★).
Frequency
Consequence
NM_024422.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.2082G>T | p.Lys694Asn | missense_variant | 13/16 | ENST00000280904.11 | |
DSC2 | NM_004949.5 | c.2082G>T | p.Lys694Asn | missense_variant | 13/17 | ||
DSC2 | NM_001406506.1 | c.1653G>T | p.Lys551Asn | missense_variant | 13/16 | ||
DSC2 | NM_001406507.1 | c.1653G>T | p.Lys551Asn | missense_variant | 13/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.2082G>T | p.Lys694Asn | missense_variant | 13/16 | 1 | NM_024422.6 | P1 | |
DSC2 | ENST00000251081.8 | c.2082G>T | p.Lys694Asn | missense_variant | 13/17 | 1 | |||
DSC2 | ENST00000648081.1 | c.1653G>T | p.Lys551Asn | missense_variant | 14/17 | ||||
DSC2 | ENST00000682357.1 | c.1653G>T | p.Lys551Asn | missense_variant | 13/16 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251104Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135718
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461828Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727218
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74334
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 | Nov 07, 2012 | The Lys694Asn variant in DSC2 has not been reported in the literature nor previo usly identified by our laboratory. This variant has not been identified in large and broad European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT ) suggest that the variant may not impact the protein, though this information i s not predictive enough to rule out pathogenicity. In summary, additional inform ation is needed to fully assess the variant's clinical significance. - |
Arrhythmogenic right ventricular dysplasia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2023 | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 46176). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs397517397, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 694 of the DSC2 protein (p.Lys694Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at