rs201948500
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_016008.4(DYNC2LI1):āc.349C>Gā(p.Leu117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.000067 ( 0 hom. )
Consequence
DYNC2LI1
NM_016008.4 missense
NM_016008.4 missense
Scores
2
10
7
Clinical Significance
Conservation
PhyloP100: 1.93
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-43794485-C-G is Pathogenic according to our data. Variant chr2-43794485-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 212765.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2LI1 | NM_016008.4 | c.349C>G | p.Leu117Val | missense_variant | 6/13 | ENST00000260605.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2LI1 | ENST00000260605.12 | c.349C>G | p.Leu117Val | missense_variant | 6/13 | 1 | NM_016008.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152064Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250730Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135552
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GnomAD4 exome AF: 0.0000671 AC: 98AN: 1461094Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 726830
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74392
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Asphyxiating thoracic dystrophy 1 Pathogenic:2
Pathogenic, no assertion criteria provided | research | David Geffen School of Medicine, University of California, Los Angeles | - | - - |
Pathogenic, no assertion criteria provided | research | David Geffen School of Medicine, University of California, Los Angeles | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 117 of the DYNC2LI1 protein (p.Leu117Val). This variant is present in population databases (rs201948500, gnomAD 0.01%). This missense change has been observed in individual(s) with short-rib thoracic dysplasia (PMID: 26077881, 32815859). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 212765). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. - |
Short-rib thoracic dysplasia 15 with polydactyly Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 16, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.
REVEL
Benign
Sift
Pathogenic
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at