rs807704

Positions:

• chr6-24300618-A-G

Variant summary

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

The NM_016356.5(DCDC2):​c.557+1097T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,206 control chromosomes in the GnomAD database, including 3,863 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 0.16 (3863 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.557+1097T>C		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.557+1097T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.557+1097T>C		intron_variant		1	NM_016356.5	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23707 AN: 152088 Hom.: 3856 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0585

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.156 AC: 23741 AN: 152206 Hom.: 3863 Cov.: 32 AF XY: 0.149 AC XY: 11125 AN XY: 74432

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.0585

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0854 Hom.: 818

Bravo AF: 0.178

Asia WGS AF: 0.0320 AC: 113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.80

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: rs807704; hg19: chr6-24300846;