rs3789220

Positions:

• chr6-24189047-G-A

Variant summary

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

The NM_016356.5(DCDC2):​c.1024-10415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 152,132 control chromosomes in the GnomAD database, including 311 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 0.050 (311 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1024-10415C>T		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1024-10415C>T		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1024-10415C>T		intron_variant		1	NM_016356.5	ENSP00000367715	P1
DCDC2	ENST00000378450.6	c.283-10415C>T		intron_variant		1		ENSP00000367711

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7600 AN: 152016 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0632

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

GnomAD4 genome AF: 0.0500 AC: 7606 AN: 152132 Hom.: 311 Cov.: 32 AF XY: 0.0534 AC XY: 3974 AN XY: 74352

Gnomad4 AFR AF: 0.0100

Gnomad4 AMR AF: 0.0755

Gnomad4 ASJ AF: 0.0328

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0477

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0434 Hom.: 41

Bravo AF: 0.0459

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.86

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: rs3789220; hg19: chr6-24189275;