Variant rs909177 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_004082.5(DCTN1):c.2016-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,614,120 control chromosomes in the GnomAD database, including 16,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1588 hom., cov: 32)

Exomes 𝑓: 0.12 ( 15159 hom. )

Consequence

DCTN1
NM_004082.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.721

Variant links:

Genes affected

DCTN1 (HGNC:2711): (dynactin subunit 1) This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. Dynactin is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit interacts with dynein intermediate chain by its domains directly binding to dynein and binds to microtubules via a highly conserved glycine-rich cytoskeleton-associated protein (CAP-Gly) domain in its N-terminus. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause distal hereditary motor neuronopathy type VIIB (HMN7B) which is also known as distal spinal and bulbar muscular atrophy (dSBMA). [provided by RefSeq, Oct 2008]

DCTN1 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=-0.81).

BP6

Variant 2-74367887-G-A is Benign according to our data. Variant chr2-74367887-G-A is described in ClinVar as [Benign]. Clinvar id is 259234.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTN1	NM_004082.5 linkuse as main transcript	c.2016-23C>T		intron_variant		ENST00000628224.3	NP_004073.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTN1	ENST00000628224.3 linkuse as main transcript	c.2016-23C>T		intron_variant		5	NM_004082.5	ENSP00000487279	A1	Q14203-1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19195

AN:

152124

Hom.:

1584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.141

AC:

35464

AN:

250790

Hom.:

3799

AF XY:

0.144

AC XY:

19505

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0756

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.469

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.124

AC:

181682

AN:

1461878

Hom.:

15159

Cov.:

AF XY:

0.127

AC XY:

92266

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.0817

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.520

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.126

AC:

19202

AN:

152242

Hom.:

1588

Cov.:

AF XY:

0.129

AC XY:

9622

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.107

Gnomad4 ASJ

AF:

0.113

Gnomad4 EAS

AF:

0.457

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.115

Hom.:

632

Bravo

AF:

0.129

Asia WGS

AF:

0.320

AC:

1109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Sep 28, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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