Variant 6-24174727-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016356.5(DCDC2):c.*3C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 1,604,766 control chromosomes in the GnomAD database, including 541,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 43068 hom., cov: 31)

Exomes 𝑓: 0.83 ( 498774 hom. )

Consequence

DCDC2
NM_016356.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.113

Variant links:

Genes affected

DCDC2 (HGNC:18141): (doublecortin domain containing 2) This gene encodes a doublecortin domain-containing family member. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. This family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. Mutations in this gene have been associated with reading disability (RD) type 2, also referred to as developmental dyslexia. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2013]

DCDC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-24174727-G-C is Benign according to our data. Variant chr6-24174727-G-C is described in ClinVar as [Benign]. Clinvar id is 1230061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24174727-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5 linkuse as main transcript	c.*3C>G		3_prime_UTR_variant	10/10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2 linkuse as main transcript	c.*3C>G		3_prime_UTR_variant	11/11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454 linkuse as main transcript	c.*3C>G		3_prime_UTR_variant	10/10	1	NM_016356.5	ENSP00000367715.3		Q9UHG0-1
DCDC2	ENST00000378450 linkuse as main transcript	c.*3C>G		3_prime_UTR_variant	3/3	1		ENSP00000367711.3		Q9UHG0-2

Frequencies

GnomAD3 genomes

AF:

0.733

AC:

111278

AN:

151886

Hom.:

43045

Cov.:

show subpopulations

Gnomad AFR

AF:

0.467

Gnomad AMI

AF:

0.740

Gnomad AMR

AF:

0.785

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.973

Gnomad SAS

AF:

0.886

Gnomad FIN

AF:

0.937

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.819

Gnomad OTH

AF:

0.712

GnomAD3 exomes

AF:

0.830

AC:

208227

AN:

250822

Hom.:

88115

AF XY:

0.836

AC XY:

113329

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.459

Gnomad AMR exome

AF:

0.867

Gnomad ASJ exome

AF:

0.766

Gnomad EAS exome

AF:

0.975

Gnomad SAS exome

AF:

0.884

Gnomad FIN exome

AF:

0.936

Gnomad NFE exome

AF:

0.821

Gnomad OTH exome

AF:

0.813

GnomAD4 exome

AF:

0.825

AC:

1199070

AN:

1452762

Hom.:

498774

Cov.:

AF XY:

0.828

AC XY:

598692

AN XY:

723328

show subpopulations

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.857

Gnomad4 ASJ exome

AF:

0.768

Gnomad4 EAS exome

AF:

0.978

Gnomad4 SAS exome

AF:

0.880

Gnomad4 FIN exome

AF:

0.931

Gnomad4 NFE exome

AF:

0.823

Gnomad4 OTH exome

AF:

0.807

GnomAD4 genome

AF:

0.733

AC:

111354

AN:

152004

Hom.:

43068

Cov.:

AF XY:

0.743

AC XY:

55234

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.467

Gnomad4 AMR

AF:

0.785

Gnomad4 ASJ

AF:

0.777

Gnomad4 EAS

AF:

0.973

Gnomad4 SAS

AF:

0.885

Gnomad4 FIN

AF:

0.937

Gnomad4 NFE

AF:

0.819

Gnomad4 OTH

AF:

0.715

Alfa

AF:

0.790

Hom.:

15575

Bravo

AF:

0.707

Asia WGS

AF:

0.902

AC:

3134

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Isolated neonatal sclerosing cholangitis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Autosomal recessive nonsyndromic hearing loss 66

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

- -

Nephronophthisis 19

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.1

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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