Variant rs745930390 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016008.4(DYNC2LI1):c.619C>G(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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DYNC2LI1
NM_016008.4 missense

Scores

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]

DYNC2LI1 links:

DYNC2LI1 (HGNC:):

DYNC2LI1 links:

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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 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	8/13	ENST00000260605.12	NP_057092.2	Q8TCX1-1
DYNC2LI1	NM_001348913.2 linkuse as main transcript	c.622C>G	p.Arg208Gly	missense_variant	8/14		NP_001335842.1
DYNC2LI1	NM_001348912.2 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	8/14		NP_001335841.1
DYNC2LI1	NM_001193464.2 linkuse as main transcript	c.622C>G	p.Arg208Gly	missense_variant	8/13		NP_001180393.1	Q8TCX1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DYNC2LI1	ENST00000260605.12 linkuse as main transcript	c.619C>G	p.Arg207Gly	missense_variant	8/13	1	NM_016008.4	ENSP00000260605.8	Q8TCX1-1
DYNC2LI1	ENST00000605786.5 linkuse as main transcript	c.622C>G	p.Arg208Gly	missense_variant	8/13	1		ENSP00000474032.1	Q8TCX1-2
DYNC2LI1	ENST00000378587.3 linkuse as main transcript	c.568C>G	p.Arg190Gly	missense_variant	7/11	1		ENSP00000367850.3	H7BYC8
DYNC2LI1	ENST00000489222.6 linkuse as main transcript	n.575C>G		non_coding_transcript_exon_variant	7/8	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

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:

AN:

1461338

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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:

AN:

152148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

D;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

2.9

M;.

PrimateAI

Uncertain

0.67

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over