Variant chr2-43776960-T-G 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.126+61T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 871,672 control chromosomes in the GnomAD database, including 13,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3009 hom., cov: 33)

Exomes 𝑓: 0.17 ( 10810 hom. )

Consequence

DYNC2LI1
NM_016008.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.99

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-43776960-T-G is Benign according to our data. Variant chr2-43776960-T-G is described in ClinVar as [Benign]. Clinvar id is 1262547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 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.126+61T>G		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.126+61T>G		intron_variant		1	NM_016008.4	ENSP00000260605	P4	Q8TCX1-1

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28912

AN:

152072

Hom.:

2995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.0211

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.200

GnomAD4 exome

AF:

0.168

AC:

120680

AN:

719480

Hom.:

10810

AF XY:

0.171

AC XY:

65148

AN XY:

380988

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.136

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.0170

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.169

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.190

AC:

28957

AN:

152192

Hom.:

3009

Cov.:

AF XY:

0.189

AC XY:

14068

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.0212

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.170

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.182

Hom.:

332

Bravo

AF:

0.190

Asia WGS

AF:

0.142

AC:

493

AN:

3464

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

-0.80

CADD

Benign

7.9

DANN

Benign

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over