rs10498720

chr6-24353208-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016356.5(DCDC2):c.348+361T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 449,126 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.045 (355 hom., cov: 33)
  • Exomes 𝑓: 0.070 (1329 hom.)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.348+361T>G		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.348+361T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.348+361T>G		intron_variant		1	NM_016356.5	P1
DCDC2	ENST00000436313.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6860 AN: 152186 Hom.: 350 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0492

GnomAD4 exome AF: 0.0700 AC: 20778 AN: 296822 Hom.: 1329 Cov.: 0 AF XY: 0.0773 AC XY: 12983 AN XY: 167896

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.0557

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0315

Gnomad4 OTH exome AF: 0.0639

GnomAD4 genome AF: 0.0451 AC: 6869 AN: 152304 Hom.: 355 Cov.: 33 AF XY: 0.0496 AC XY: 3690 AN XY: 74466

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0329

Gnomad4 OTH AF: 0.0567

Alfa AF: 0.0389 Hom.: 72

Bravo AF: 0.0455

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.5
Dann	Benign	0.60

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: rs10498720; hg19: chr6-24353436; COSMIC: COSV51239694; COSMIC: COSV51239694;