rs6456605

Positions:

• chr6-24336788-C-A

Variant summary

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

The NM_016356.5(DCDC2):​c.348+16781G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,682 control chromosomes in the GnomAD database, including 9,586 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 0.32 (9586 hom., cov: 31)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.348+16781G>T		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.348+16781G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.348+16781G>T		intron_variant		1	NM_016356.5	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49136 AN: 151566 Hom.: 9570 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.324 AC: 49197 AN: 151682 Hom.: 9586 Cov.: 31 AF XY: 0.318 AC XY: 23592 AN XY: 74106

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.318

Alfa AF: 0.272 Hom.: 1253

Bravo AF: 0.342

Asia WGS AF: 0.206 AC: 715 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.30

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: rs6456605; hg19: chr6-24337016;