rs745930390
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The ENST00000260605.12(DYNC2LI1):āc.619C>Gā(p.Arg207Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
DYNC2LI1
ENST00000260605.12 missense
ENST00000260605.12 missense
Scores
12
6
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.95
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.959
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYNC2LI1 | NM_016008.4 | c.619C>G | p.Arg207Gly | missense_variant | 8/13 | ENST00000260605.12 | NP_057092.2 | |
DYNC2LI1 | NM_001348913.2 | c.622C>G | p.Arg208Gly | missense_variant | 8/14 | NP_001335842.1 | ||
DYNC2LI1 | NM_001348912.2 | c.619C>G | p.Arg207Gly | missense_variant | 8/14 | NP_001335841.1 | ||
DYNC2LI1 | NM_001193464.2 | c.622C>G | p.Arg208Gly | missense_variant | 8/13 | NP_001180393.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC2LI1 | ENST00000260605.12 | c.619C>G | p.Arg207Gly | missense_variant | 8/13 | 1 | NM_016008.4 | ENSP00000260605 | P4 | |
DYNC2LI1 | ENST00000605786.5 | c.622C>G | p.Arg208Gly | missense_variant | 8/13 | 1 | ENSP00000474032 | A1 | ||
DYNC2LI1 | ENST00000378587.3 | c.571C>G | p.Arg191Gly | missense_variant | 7/11 | 1 | ENSP00000367850 | |||
DYNC2LI1 | ENST00000489222.6 | n.575C>G | non_coding_transcript_exon_variant | 7/8 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461338Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726978
GnomAD4 exome
AF:
AC:
1
AN:
1461338
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
726978
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74320
GnomAD4 genome
AF:
AC:
1
AN:
152148
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74320
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0151);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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