NM_001080463.2:c.11734_11737delAGAC
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001080463.2(DYNC2H1):c.11734_11737delAGAC(p.Arg3912PhefsTer26) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
DYNC2H1
NM_001080463.2 frameshift
NM_001080463.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.36
Publications
1 publications found
Genes affected
DYNC2H1 (HGNC:2962): (dynein cytoplasmic 2 heavy chain 1) This gene encodes a large cytoplasmic dynein protein that is involved in retrograde transport in the cilium and has a role in intraflagellar transport, a process required for ciliary/flagellar assembly. Mutations in this gene cause a heterogeneous spectrum of conditions related to altered primary cilium function and often involve polydactyly, abnormal skeletogenesis, and polycystic kidneys. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jan 2010]
DYNC2H1 Gene-Disease associations (from GenCC):
- asphyxiating thoracic dystrophy 3Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, ClinGen
- Jeune syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- short rib-polydactyly syndrome, Majewski typeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- short rib-polydactyly syndrome, Verma-Naumoff typeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-103316604-TGACA-T is Pathogenic according to our data. Variant chr11-103316604-TGACA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 446583.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001080463.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DYNC2H1 | MANE Plus Clinical | c.11734_11737delAGAC | p.Arg3912PhefsTer26 | frameshift | Exon 81 of 90 | ENSP00000497174.1 | Q8NCM8-2 | ||
| DYNC2H1 | TSL:1 MANE Select | c.11713_11716delAGAC | p.Arg3905PhefsTer26 | frameshift | Exon 80 of 89 | ENSP00000364887.2 | Q8NCM8-1 | ||
| DYNC2H1 | TSL:1 | c.2206-119335_2206-119332delAGAC | intron | N/A | ENSP00000334021.7 | Q8NCM8-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
2
-
-
Asphyxiating thoracic dystrophy 3 (2)
1
-
-
Jeune thoracic dystrophy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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