6-24174727-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.113

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]

ACMG classification

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	UniProt
DCDC2	NM_016356.5	c.*3C>G		3_prime_UTR_variant	10/10	ENST00000378454.8
DCDC2	NM_001195610.2	c.*3C>G		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.*3C>G		3_prime_UTR_variant	10/10	1	NM_016356.5	P1
DCDC2	ENST00000378450.6	c.*3C>G		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111278 AN: 151886 Hom.: 43045 Cov.: 31

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

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.: 28 AF XY: 0.828 AC XY: 598692 AN XY: 723328

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.: 31 AF XY: 0.743 AC XY: 55234 AN XY: 74326

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

Submissions by phenotype

Isolated neonatal sclerosing cholangitis 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

- -

Autosomal recessive nonsyndromic hearing loss 66 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

Other links and lift over

dbSNP: rs9358755; hg19: chr6-24174955;