rs793720

Positions:

• chr6-24353052-G-A
• chr6-24353052-G-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+517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,110 control chromosomes in the GnomAD database, including 25,358 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 0.55 (25358 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.348+517C>T		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.348+517C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.348+517C>T		intron_variant		1	NM_016356.5	P1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84101 AN: 151994 Hom.: 25343 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.563

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.553 AC: 84129 AN: 152110 Hom.: 25358 Cov.: 33 AF XY: 0.558 AC XY: 41509 AN XY: 74354

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.568

Alfa AF: 0.618 Hom.: 7913

Bravo AF: 0.548

Asia WGS AF: 0.710 AC: 2471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs793720; hg19: chr6-24353280;