rs745930390

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000260605.12(DYNC2LI1):ā€‹c.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

Scores

12
6
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.95
Variant links:
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
DYNC2LI1NM_016008.4 linkuse as main transcriptc.619C>G p.Arg207Gly missense_variant 8/13 ENST00000260605.12 NP_057092.2
DYNC2LI1NM_001348913.2 linkuse as main transcriptc.622C>G p.Arg208Gly missense_variant 8/14 NP_001335842.1
DYNC2LI1NM_001348912.2 linkuse as main transcriptc.619C>G p.Arg207Gly missense_variant 8/14 NP_001335841.1
DYNC2LI1NM_001193464.2 linkuse as main transcriptc.622C>G p.Arg208Gly missense_variant 8/13 NP_001180393.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DYNC2LI1ENST00000260605.12 linkuse as main transcriptc.619C>G p.Arg207Gly missense_variant 8/131 NM_016008.4 ENSP00000260605 P4Q8TCX1-1
DYNC2LI1ENST00000605786.5 linkuse as main transcriptc.622C>G p.Arg208Gly missense_variant 8/131 ENSP00000474032 A1Q8TCX1-2
DYNC2LI1ENST00000378587.3 linkuse as main transcriptc.571C>G p.Arg191Gly missense_variant 7/111 ENSP00000367850
DYNC2LI1ENST00000489222.6 linkuse as main transcriptn.575C>G non_coding_transcript_exon_variant 7/83

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461338
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.68
D;.
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.96
D;D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Pathogenic
2.9
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-6.3
D;.
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.99
MutPred
0.84
Loss of MoRF binding (P = 0.0151);.;
MVP
0.51
MPC
0.30
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.89
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745930390; hg19: chr2-44023899; API