rs372979057
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_024422.6(DSC2):c.1520+8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_024422.6 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.1520+8C>G | splice_region_variant, intron_variant | ENST00000280904.11 | |||
DSC2 | NM_001406506.1 | c.1091+8C>G | splice_region_variant, intron_variant | ||||
DSC2 | NM_001406507.1 | c.1091+8C>G | splice_region_variant, intron_variant | ||||
DSC2 | NM_004949.5 | c.1520+8C>G | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.1520+8C>G | splice_region_variant, intron_variant | 1 | NM_024422.6 | P1 | |||
DSC2 | ENST00000251081.8 | c.1520+8C>G | splice_region_variant, intron_variant | 1 | |||||
DSC2 | ENST00000648081.1 | c.1091+8C>G | splice_region_variant, intron_variant | ||||||
DSC2 | ENST00000682357.1 | c.1091+8C>G | splice_region_variant, intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 250960Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135684
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461500Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 727060
GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17AN XY: 74322
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Arrhythmogenic right ventricular dysplasia 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Oct 24, 2017 | - - |
DSC2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 06, 2019 | 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). - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at