Variant chr2-43783481-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016008.4(DYNC2LI1):c.127-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,436,768 control chromosomes in the GnomAD database, including 90,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15598 hom., cov: 32)

Exomes 𝑓: 0.33 ( 74606 hom. )

Consequence

DYNC2LI1
NM_016008.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0840

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-43783481-G-A is Benign according to our data. Variant chr2-43783481-G-A is described in ClinVar as [Benign]. Clinvar id is 1294721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2LI1	NM_016008.4 linkuse as main transcript	c.127-39G>A		intron_variant		ENST00000260605.12	NP_057092.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2LI1	ENST00000260605.12 linkuse as main transcript	c.127-39G>A		intron_variant		1	NM_016008.4	ENSP00000260605	P4	Q8TCX1-1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64409

AN:

151890

Hom.:

15549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.662

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.410

GnomAD3 exomes

AF:

0.358

AC:

66464

AN:

185582

Hom.:

13074

AF XY:

0.356

AC XY:

36366

AN XY:

102088

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.463

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.320

Gnomad OTH exome

AF:

0.348

GnomAD4 exome

AF:

0.331

AC:

425833

AN:

1284760

Hom.:

74606

Cov.:

AF XY:

0.335

AC XY:

215576

AN XY:

643782

show subpopulations

Gnomad4 AFR exome

AF:

0.669

Gnomad4 AMR exome

AF:

0.451

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.162

Gnomad4 SAS exome

AF:

0.466

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.424

AC:

64509

AN:

152008

Hom.:

15598

Cov.:

AF XY:

0.422

AC XY:

31376

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.663

Gnomad4 AMR

AF:

0.453

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.460

Gnomad4 FIN

AF:

0.298

Gnomad4 NFE

AF:

0.316

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.355

Hom.:

2764

Bravo

AF:

0.443

Asia WGS

AF:

0.355

AC:

1233

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.0

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over