Variant 2-74377768-T-C 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.280-42A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,579,042 control chromosomes in the GnomAD database, including 13,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1357 hom., cov: 32)

Exomes 𝑓: 0.10 ( 11877 hom. )

Consequence

DCTN1
NM_004082.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.85

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:

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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=-0.72).

BP6

Variant 2-74377768-T-C is Benign according to our data. Variant chr2-74377768-T-C is described in ClinVar as [Benign]. Clinvar id is 259237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-74377768-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCTN1	NM_004082.5 linkuse as main transcript	c.280-42A>G		intron_variant		ENST00000628224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCTN1	ENST00000628224.3 linkuse as main transcript	c.280-42A>G		intron_variant		5	NM_004082.5	A1	Q14203-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16888

AN:

152074

Hom.:

1355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.0879

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.0948

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0786

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.126

AC:

31535

AN:

250234

Hom.:

3415

AF XY:

0.129

AC XY:

17439

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0605

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.471

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.0951

Gnomad NFE exome

AF:

0.0804

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.102

AC:

145412

AN:

1426850

Hom.:

11877

Cov.:

AF XY:

0.105

AC XY:

74658

AN XY:

712266

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.0656

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.521

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.0968

Gnomad4 NFE exome

AF:

0.0795

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.111

AC:

16895

AN:

152192

Hom.:

1357

Cov.:

AF XY:

0.115

AC XY:

8578

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0877

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.458

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.0948

Gnomad4 NFE

AF:

0.0786

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0934

Hom.:

184

Bravo

AF:

0.112

Asia WGS

AF:

0.326

AC:

1128

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.9

DANN

Benign

0.83

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