rs9460976

chr6-24212892-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.923-7790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,154 control chromosomes in the GnomAD database, including 1,004 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 0.11 (1004 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.923-7790C>T		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.923-7790C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.923-7790C>T		intron_variant		1	NM_016356.5	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16721 AN: 152036 Hom.: 1004 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.0904

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0488

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.110 AC: 16737 AN: 152154 Hom.: 1004 Cov.: 32 AF XY: 0.106 AC XY: 7878 AN XY: 74372

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0903

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0488

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.127

Alfa AF: 0.118 Hom.: 235

Bravo AF: 0.115

Asia WGS AF: 0.0820 AC: 284 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.022
Dann	Benign	0.39

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: rs9460976; hg19: chr6-24213120;