Genetic Variant DCDC1:p.Glu1563Lys (chr11-30899619-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_001387274.1(DCDC1):c.4687G>A(p.Glu1563Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,567,600 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 9 hom., cov: 32)

Exomes 𝑓: 0.011 ( 85 hom. )

Consequence

DCDC1
NM_001387274.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.169

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:

LOC105376611 (HGNC:):

LOC105376611 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=0.0050623417).

BP6

Variant 11-30899619-C-T is Benign according to our data. Variant chr11-30899619-C-T is described in ClinVar as [Benign]. Clinvar id is 2641698.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC1	NM_001387274.1 link	c.4687G>A	p.Glu1563Lys	missense_variant	Exon 34 of 39	ENST00000684477.1	NP_001374203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC1	ENST00000684477.1 link	c.4687G>A	p.Glu1563Lys	missense_variant	Exon 34 of 39		NM_001387274.1	ENSP00000507427.1		A0A804HJA9

Frequencies

GnomAD3 genomes

AF:

0.00853

AC:

1297

AN:

152004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00925

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00752

AC:

1499

AN:

199286

Hom.:

AF XY:

0.00795

AC XY:

850

AN XY:

106860

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00440

Gnomad FIN exome

AF:

0.00942

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0109

AC:

15446

AN:

1415478

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

7653

AN XY:

701212

show subpopulations

Gnomad4 AFR exome

AF:

0.00202

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.00216

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00455

Gnomad4 FIN exome

AF:

0.0109

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.00920

GnomAD4 genome

AF:

0.00853

AC:

1297

AN:

152122

Hom.:

Cov.:

AF XY:

0.00828

AC XY:

616

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00246

Gnomad4 AMR

AF:

0.00924

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00766

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.00686

AC:

829

Asia WGS

AF:

0.00318

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DCDC5-related condition

Benign:1

May 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided

Benign:1

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DCDC1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.4

DANN

Benign

0.89

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.33

REVEL

Benign

0.0050

Sift4G

Benign

0.61

T;T

Vest4

0.12

MVP

0.34

ClinPred

0.0076

GERP RS

1.6

gMVP

0.11

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