DSC2 c.154+2T>C
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,602,850)
Conditions
2
cardiomyopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +2 | canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.94 | donor loss · deltas |
| Pangolin | Δ0.83 | loss · gain 0.08 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2, phastCons 1 |
| Non-coding constraint | Z -1.27 | 1 kb window · o/e 1.10 · regional · uncalibrated |
| Overall | ||
| CADD | 25.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,602,850). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- DSC2
- Coding
- c.154+2T>C
- MANE Select
- NM_024422
- dbSNP
- rs747424133
- Type
- single nucleotide variant
- Location
- chr18:31093557 (GRCh38)
- Gene constraint
- LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.26 · 3 PDB
Similar variants
- DSC2 c.1664-1G>A Likely pathogenic ★★ same condition
- DSC2 c.354+2T>A Likely pathogenic ★★ same condition
- DSC2 c.355-1G>A Likely pathogenic ★★ same condition
- DSC2 p.Gln554Ter Pathogenic ★★ same condition
- DSC2 p.Gln620Ter Pathogenic ★★ same condition
- DSC2 p.Glu127Ter Pathogenic/Likely pathogenic ★★ same condition
- DSC2 p.Glu593Ter Pathogenic ★★ same condition
- DSC2 p.Ser740Ter Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dsc2-c-154-plus-2t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown