6-24250283-T-C

Variant names:

• chr6-24250283-T-C
• rs9295619
• NM_016356.5:c.922+27766A>G

Variant summary

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

The NM_016356.5(DCDC2):​c.922+27766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,972 control chromosomes in the GnomAD database, including 20,299 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 0.48 (20299 hom., cov: 31)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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 (NFE) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.922+27766A>G		intron_variant	Intron 7 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.922+27766A>G		intron_variant	Intron 8 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.922+27766A>G		intron_variant	Intron 7 of 9	1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72430 AN: 151854 Hom.: 20296 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.477 AC: 72447 AN: 151972 Hom.: 20299 Cov.: 31 AF XY: 0.483 AC XY: 35869 AN XY: 74276

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.496

Alfa AF: 0.561 Hom.: 18126

Bravo AF: 0.450

Asia WGS AF: 0.459 AC: 1600 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	3.4
DANN	Benign	0.61

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: rs9295619; hg19: chr6-24250511;