rs870601

chr6-24260832-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.922+17217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,158 control chromosomes in the GnomAD database, including 27,533 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 0.56 (27533 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.922+17217A>G		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.922+17217A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.922+17217A>G		intron_variant		1	NM_016356.5	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84991 AN: 152040 Hom.: 27527 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.559 AC: 85023 AN: 152158 Hom.: 27533 Cov.: 32 AF XY: 0.569 AC XY: 42328 AN XY: 74380

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.573

Alfa AF: 0.663 Hom.: 41319

Bravo AF: 0.532

Asia WGS AF: 0.711 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.015
Dann	Benign	0.66

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: rs870601; hg19: chr6-24261060;