rs1087291

Positions:

• chr6-24200181-A-G
• chr6-24200181-A-T

Variant summary

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

The NM_016356.5(DCDC2):​c.1023+4821T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,038 control chromosomes in the GnomAD database, including 18,716 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 0.45 (18716 hom., cov: 31)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.1023+4821T>C		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.1023+4821T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.1023+4821T>C		intron_variant		1	NM_016356.5	P1
DCDC2	ENST00000378450.6	c.282+4821T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68430 AN: 151920 Hom.: 18714 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.450 AC: 68437 AN: 152038 Hom.: 18716 Cov.: 31 AF XY: 0.456 AC XY: 33917 AN XY: 74314

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.409

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.455

Alfa AF: 0.500 Hom.: 2576

Bravo AF: 0.423

Asia WGS AF: 0.423 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1087291; hg19: chr6-24200409;