Genetic Variant DCDC1:p.Ala1431Thr (chr11-30904978-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001387274.1(DCDC1):c.4291G>A(p.Ala1431Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,613,726 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 59 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 54 hom. )

Consequence

DCDC1
NM_001387274.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.59

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063848794).

BP6

Variant 11-30904978-C-T is Benign according to our data. Variant chr11-30904978-C-T is described in ClinVar as [Benign]. Clinvar id is 718776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC1	NM_001387274.1 link	c.4291G>A	p.Ala1431Thr	missense_variant	Exon 31 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.4291G>A	p.Ala1431Thr	missense_variant	Exon 31 of 39		NM_001387274.1	ENSP00000507427.1		A0A804HJA9

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2246

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0518

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00387

AC:

961

AN:

248508

Hom.:

AF XY:

0.00271

AC XY:

365

AN XY:

134510

show subpopulations

Gnomad AFR exome

AF:

0.0509

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000307

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00155

AC:

2264

AN:

1461452

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

943

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.0502

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000186

Gnomad4 OTH exome

AF:

0.00350

GnomAD4 genome

AF:

0.0148

AC:

2253

AN:

152274

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1042

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0518

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.0161

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0475

AC:

209

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00468

AC:

568

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

DCDC5-related condition

Benign:1

May 28, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0064

T;T

MetaSVM

Uncertain

0.10

PrimateAI

Benign

0.44

REVEL

Uncertain

0.49

Sift4G

Pathogenic

0.0

D;D

Vest4

0.70

MVP

0.78

ClinPred

0.014

GERP RS

5.3

gMVP

0.091

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