Variant chr12-57532803-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001261413.2(DCTN2):c.782T>C(p.Val261Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000615 in 1,613,972 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 7 hom. )

Consequence

DCTN2
NM_001261413.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.43

Variant links:

Genes affected

DCTN2 (HGNC:2712): (dynactin subunit 2) This gene encodes a 50-kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It 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 is present in 4-5 copies per dynactin molecule. It contains three short alpha-helical coiled-coil domains that may mediate association with self or other dynactin subunits. It may interact directly with the largest subunit (p150) of dynactin and may affix p150 in place. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2012]

DCTN2 links:

DCTN2 (HGNC:):

DCTN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029218584).

BP6

Variant 12-57532803-A-G is Benign according to our data. Variant chr12-57532803-A-G is described in ClinVar as [Benign]. Clinvar id is 2643137.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 98 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTN2	NM_001261413.2 linkuse as main transcript	c.782T>C	p.Val261Ala	missense_variant	10/14	ENST00000548249.6	NP_001248342.1	Q13561-1A0A384MDU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTN2	ENST00000548249.6 linkuse as main transcript	c.782T>C	p.Val261Ala	missense_variant	10/14	1	NM_001261413.2	ENSP00000447824.1		Q13561-1

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000899

AC:

224

AN:

249222

Hom.:

AF XY:

0.000917

AC XY:

124

AN XY:

135200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.000876

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000612

AC:

894

AN:

1461704

Hom.:

Cov.:

AF XY:

0.000642

AC XY:

467

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00178

Gnomad4 NFE exome

AF:

0.000517

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.000644

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000472

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000483

AC:

ExAC

AF:

0.000811

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

DCTN2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

T;.;.;.;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.0055

MetaRNN

Benign

0.029

T;T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.9

L;.;.;.;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

N;N;N;.;N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

D;D;D;.;T;T

Sift4G

Benign

0.25

T;T;D;T;T;T

Polyphen

0.94

P;.;.;.;.;.

Vest4

0.76

MVP

0.33

MPC

0.60

ClinPred

0.055

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.24

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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