Variant 11-31077909-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001387274.1(DCDC1):c.2254T>G(p.Ser752Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 766,240 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 0 hom. )

Consequence

DCDC1
NM_001387274.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.40

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008241147).

BP6

Variant 11-31077909-A-C is Benign according to our data. Variant chr11-31077909-A-C is described in ClinVar as [Benign]. Clinvar id is 3043008.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00455 (693/152346) while in subpopulation AFR AF= 0.016 (666/41578). AF 95% confidence interval is 0.015. There are 7 homozygotes in gnomad4. There are 328 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC1	NM_001387274.1 linkuse as main transcript	c.2254T>G	p.Ser752Ala	missense_variant	18/39	ENST00000684477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC1	ENST00000684477.1 linkuse as main transcript	c.2254T>G	p.Ser752Ala	missense_variant	18/39		NM_001387274.1	A2
DCDC1	ENST00000597505.5 linkuse as main transcript	c.2254T>G	p.Ser752Ala	missense_variant	16/36	5		A2	M0R2J8-1
DCDC1	ENST00000437348.5 linkuse as main transcript	n.962T>G		non_coding_transcript_exon_variant	8/12	5
DCDC1	ENST00000342355.8 linkuse as main transcript	c.*1329T>G		3_prime_UTR_variant, NMD_transcript_variant	18/22	2			M0R2J8-2

Frequencies

GnomAD3 genomes

AF:

0.00454

AC:

691

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00105

AC:

246

AN:

234080

Hom.:

AF XY:

0.000774

AC XY:

AN XY:

127956

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000918

Gnomad OTH exome

AF:

0.000849

GnomAD4 exome

AF:

0.000521

AC:

320

AN:

613894

Hom.:

Cov.:

AF XY:

0.000396

AC XY:

133

AN XY:

335478

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.000480

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000287

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000286

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00455

AC:

693

AN:

152346

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

328

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00283

Hom.:

Bravo

AF:

0.00505

ESP6500AA

AF:

0.0130

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00120

AC:

143

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DCDC1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 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

Benign

0.090

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.87

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0082

PrimateAI

Benign

0.38

Sift4G

Benign

0.61

Vest4

0.29

MVP

0.59

GERP RS

4.3

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