rs1555639038
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024422.6(DSC2):c.1078-6T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,146 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 predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024422.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSC2 | NM_024422.6 | c.1078-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000280904.11 | |||
DSC2 | NM_001406506.1 | c.649-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
DSC2 | NM_001406507.1 | c.649-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
DSC2 | NM_004949.5 | c.1078-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSC2 | ENST00000280904.11 | c.1078-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_024422.6 | P1 | |||
DSC2 | ENST00000251081.8 | c.1078-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
DSC2 | ENST00000648081.1 | c.649-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||||
DSC2 | ENST00000682357.1 | c.649-6T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460146Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726426
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Arrhythmogenic right ventricular dysplasia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 22, 2023 | 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. This sequence change falls in intron 8 of the DSC2 gene. It does not directly change the encoded amino acid sequence of the DSC2 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 468368). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at