Variant 11-30931781-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001387275.1(DCDC1):c.-415C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,610,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 1 hom. )

Consequence

DCDC1
NM_001387275.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034106016).

BP6

Variant 11-30931781-G-A is Benign according to our data. Variant chr11-30931781-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3080416.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC1	NM_001387274.1 linkuse as main transcript	c.2887C>T	p.Arg963Trp	missense_variant	22/39	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.2887C>T	p.Arg963Trp	missense_variant	22/39		NM_001387274.1	ENSP00000507427.1		A0A804HJA9

Frequencies

GnomAD3 genomes

AF:

0.000737

AC:

112

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000505

AC:

124

AN:

245526

Hom.:

AF XY:

0.000414

AC XY:

AN XY:

132938

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00103

AC:

1498

AN:

1457878

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

743

AN XY:

725222

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.000539

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.000499

GnomAD4 genome

AF:

0.000736

AC:

112

AN:

152130

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000695

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000470

AC:

EpiCase

AF:

0.000716

EpiControl

AF:

0.000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.17

DANN

Benign

0.86

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-0.53

PrimateAI

Benign

0.20

Sift4G

Benign

0.12

T;T

Vest4

0.18

MVP

0.42

ClinPred

0.061

GERP RS

-1.7

gMVP

0.27

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