Variant 2-43805249-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_016008.4(DYNC2LI1):c.993+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

DYNC2LI1
NM_016008.4 splice_region, intron

Scores

Splicing: ADA: 0.9963

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 1.93

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-43805249-A-G is Pathogenic according to our data. Variant chr2-43805249-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 212768.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DYNC2LI1	NM_016008.4 linkuse as main transcript	c.993+3A>G	splice_region_variant, intron_variant	ENST00000260605.12	NP_057092.2	Q8TCX1-1
DYNC2LI1	NM_001348913.2 linkuse as main transcript	c.996+3A>G	splice_region_variant, intron_variant		NP_001335842.1
DYNC2LI1	NM_001348912.2 linkuse as main transcript	c.993+3A>G	splice_region_variant, intron_variant		NP_001335841.1
DYNC2LI1	NM_001193464.2 linkuse as main transcript	c.996+3A>G	splice_region_variant, intron_variant		NP_001180393.1	Q8TCX1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DYNC2LI1	ENST00000378587.3 linkuse as main transcript	c.945A>G	p.Val315Val	synonymous_variant	11/11	1		ENSP00000367850.3	H7BYC8
DYNC2LI1	ENST00000260605.12 linkuse as main transcript	c.993+3A>G		splice_region_variant, intron_variant		1	NM_016008.4	ENSP00000260605.8	Q8TCX1-1
DYNC2LI1	ENST00000605786.5 linkuse as main transcript	c.996+3A>G		splice_region_variant, intron_variant		1		ENSP00000474032.1	Q8TCX1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428526

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712510

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:

9.23e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Asphyxiating thoracic dystrophy 1

Pathogenic:1

Pathogenic, no assertion criteria provided

research

David Geffen School of Medicine, University of California, Los Angeles

- -

Short-rib thoracic dysplasia 15 with polydactyly

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 16, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.75

SpliceAI score (max)

0.91

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.91

Position offset: -3

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over