rs807724

Positions:

• chr6-24278641-C-T

Variant summary

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

The NM_016356.5(DCDC2):​c.760-430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,030 control chromosomes in the GnomAD database, including 40,307 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 0.71 (40307 hom., cov: 30)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.760-430G>A		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.760-430G>A		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.760-430G>A		intron_variant		1	NM_016356.5	ENSP00000367715	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108329 AN: 151912 Hom.: 40294 Cov.: 30

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.713 AC: 108378 AN: 152030 Hom.: 40307 Cov.: 30 AF XY: 0.721 AC XY: 53604 AN XY: 74328

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.951

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.698

Alfa AF: 0.749 Hom.: 12436

Bravo AF: 0.692

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.75

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: rs807724; hg19: chr6-24278869; COSMIC: COSV65832155;