6-24289224-T-C

Position:

• chr6-24289224-T-C

Variant summary

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

The NM_016356.5(DCDC2):​c.705-318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,118 control chromosomes in the GnomAD database, including 25,459 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 0.52 (25459 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.705-318A>G		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.705-318A>G		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.705-318A>G		intron_variant		1	NM_016356.5	ENSP00000367715	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79763 AN: 152000 Hom.: 25455 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.524 AC: 79769 AN: 152118 Hom.: 25459 Cov.: 33 AF XY: 0.534 AC XY: 39729 AN XY: 74336

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.541

Alfa AF: 0.584 Hom.: 3604

Bravo AF: 0.496

Asia WGS AF: 0.682 AC: 2370 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.40

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: rs2296539; hg19: chr6-24289452;