rs6922023

Positions:

• chr6-24347889-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.348+5680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,034 control chromosomes in the GnomAD database, including 4,283 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 0.22 (4283 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.348+5680C>T		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.348+5680C>T		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.348+5680C>T		intron_variant		1	NM_016356.5	ENSP00000367715	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33913 AN: 151916 Hom.: 4272 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.223 AC: 33954 AN: 152034 Hom.: 4283 Cov.: 32 AF XY: 0.225 AC XY: 16743 AN XY: 74320

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.187

Alfa AF: 0.187 Hom.: 1772

Bravo AF: 0.228

Asia WGS AF: 0.282 AC: 979 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	2.0
DANN	Benign	0.58

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: rs6922023; hg19: chr6-24348117;