Variant 11-30899605-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001387274.1(DCDC1):c.4701G>C(p.Trp1567Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 1,574,150 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 5 hom. )

Consequence

DCDC1
NM_001387274.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

DCDC1 (HGNC:20625): (doublecortin domain containing 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene is a hydrophilic, intracellular protein. It contains a single doublecortin domain and is unable to bind microtubules and to regulate microtubule polymerization. This gene is mainly expressed in adult testis. It does not have a mouse homolog. [provided by RefSeq, Sep 2010]

DCDC1 links:

DCDC1 (HGNC:):

DCDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008265108).

BP6

Variant 11-30899605-C-G is Benign according to our data. Variant chr11-30899605-C-G is described in ClinVar as [Benign]. Clinvar id is 721756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC1	NM_001387274.1 linkuse as main transcript	c.4701G>C	p.Trp1567Cys	missense_variant	34/39	ENST00000684477.1	NP_001374203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC1	ENST00000684477.1 linkuse as main transcript	c.4701G>C	p.Trp1567Cys	missense_variant	34/39		NM_001387274.1	ENSP00000507427.1		A0A804HJA9

Frequencies

GnomAD3 genomes

AF:

0.00420

AC:

638

AN:

151904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.000937

AC:

200

AN:

213418

Hom.:

AF XY:

0.000662

AC XY:

AN XY:

114840

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.000829

Gnomad ASJ exome

AF:

0.000108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000386

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000642

Gnomad OTH exome

AF:

0.000376

GnomAD4 exome

AF:

0.000406

AC:

578

AN:

1422128

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

256

AN XY:

705160

show subpopulations

Gnomad4 AFR exome

AF:

0.0139

Gnomad4 AMR exome

AF:

0.000843

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000510

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.000990

GnomAD4 genome

AF:

0.00419

AC:

637

AN:

152022

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

281

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000699

Hom.:

Bravo

AF:

0.00505

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00106

AC:

128

Asia WGS

AF:

0.000869

AC:

AN:

3466

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

DCDC5-related condition

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.18

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-0.87

PrimateAI

Uncertain

0.56

REVEL

Benign

0.24

Sift4G

Uncertain

0.0020

D;D

Vest4

0.67

MVP

0.53

ClinPred

0.018

GERP RS

4.7

gMVP

0.10

Splicing

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