rs879255655
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_016008.4(DYNC2LI1):c.1000G>T(p.Glu334*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DYNC2LI1
NM_016008.4 stop_gained
NM_016008.4 stop_gained
Scores
5
2
Clinical Significance
Conservation
PhyloP100: 6.83
Publications
2 publications found
Genes affected
DYNC2LI1 (HGNC:24595): (dynein cytoplasmic 2 light intermediate chain 1) This gene encodes a protein that is a component of the dynein-2 microtubule motor protein complex that plays a role in the retrograde transport of cargo in primary cilia via the intraflagellar transport system. This gene is ubiquitously expressed and its protein, which localizes to the axoneme and Golgi apparatus, interacts directly with the cytoplasmic dynein 2 heavy chain 1 protein to form part of the multi-protein dynein-2 complex. Mutations in this gene produce defects in the dynein-2 complex which result in several types of ciliopathy including short-rib thoracic dysplasia 15 with polydactyly (SRTD15). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2017]
ABCG5 (HGNC:13886): (ATP binding cassette subfamily G member 5) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]
ABCG5 Gene-Disease associations (from GenCC):
- sitosterolemiaInheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- sitosterolemia 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
- sitosterolemia 2Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_016008.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.053 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-43809711-G-T is Pathogenic according to our data. Variant chr2-43809711-G-T is described in ClinVar as Pathogenic. ClinVar VariationId is 212767.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016008.4. 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 |
|---|---|---|---|---|---|---|---|---|---|
| DYNC2LI1 | TSL:1 MANE Select | c.1000G>T | p.Glu334* | stop_gained | Exon 13 of 13 | ENSP00000260605.8 | Q8TCX1-1 | ||
| DYNC2LI1 | TSL:1 | c.1003G>T | p.Glu335* | stop_gained | Exon 13 of 13 | ENSP00000474032.1 | Q8TCX1-2 | ||
| DYNC2LI1 | c.1120G>T | p.Glu374* | stop_gained | Exon 14 of 14 | ENSP00000635162.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1458292Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725422
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1458292
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
725422
African (AFR)
AF:
AC:
0
AN:
33346
American (AMR)
AF:
AC:
0
AN:
44250
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26054
East Asian (EAS)
AF:
AC:
0
AN:
39506
South Asian (SAS)
AF:
AC:
0
AN:
85464
European-Finnish (FIN)
AF:
AC:
0
AN:
53356
Middle Eastern (MID)
AF:
AC:
0
AN:
5682
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1110404
Other (OTH)
AF:
AC:
0
AN:
60230
GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Asphyxiating thoracic dystrophy 1 (1)
1
-
-
Short-rib thoracic dysplasia 15 with polydactyly (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
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
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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