6-24203496-T-G

Position:

• chr6-24203496-T-G

Variant summary

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

The NM_016356.5(DCDC2):​c.1023+1506A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,986 control chromosomes in the GnomAD database, including 30,519 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 0.62 (30519 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286

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 (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1023+1506A>C		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1023+1506A>C		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1023+1506A>C		intron_variant		1	NM_016356.5	ENSP00000367715	P1
DCDC2	ENST00000378450.6	c.282+1506A>C		intron_variant		1		ENSP00000367711

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94281 AN: 151868 Hom.: 30507 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.621 AC: 94327 AN: 151986 Hom.: 30519 Cov.: 32 AF XY: 0.626 AC XY: 46488 AN XY: 74310

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.627

Alfa AF: 0.635 Hom.: 3764

Bravo AF: 0.600

Asia WGS AF: 0.613 AC: 2135 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	5.7
DANN	Benign	0.79

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: rs1087294; hg19: chr6-24203724;