Is DYNC2I2 p.Ser28fs (c.82_83insCA) pathogenic?

DYNC2I2 p.Ser28fs (c.8283insCA) is classified Likely pathogenic in DYNC2I2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). Associated with short-rib thoracic dysplasia 11 with or without polydactyly.

What condition is associated with DYNC2I2 p.Ser28fs (c.82_83insCA)?

DYNC2I2 p.Ser28fs (c.82_83insCA) is associated with short-rib thoracic dysplasia 11 with or without polydactyly (ClinVar).

DYNC2I2 p.Ser28fs

c.82_83insCA · VCV3778830

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

short-rib thoracic dysplasia 11 with or without polydactyly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1	GERP -2.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DYNC2I2
Protein: p.Ser28fs
Coding: c.82_83insCA
MANE Select: NM_052844
Type: Insertion
Location: chr9:128656644 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.66 · 4 PDB

Full DYNC2I2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short-rib thoracic dysplasia 11 with or without polydactyly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYNC2I2 p.Ser28Gly Uncertain significance ★ ⚠ same residue
DYNC2I2 p.Ser28= Likely benign ★ same residue
DYNC2I2 p.Ser28Asn Uncertain significance ★ ⚠ same residue
DYNC2I2 c.187-18_187-17insTTGTA Likely benign ★ same condition
DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same condition
DYNC2I2 p.Arg121Ter Pathogenic ★★ same condition
DYNC2I2 p.Arg182Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
DYNC2I2 p.Arg447Trp Pathogenic/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/dync2i2-p-ser28fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown