6-24256498-G-A

Position:

• chr6-24256498-G-A

Variant summary

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

The ENST00000378454.8(DCDC2):​c.922+21551C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 152,188 control chromosomes in the GnomAD database, including 66,616 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 0.93 (66616 hom., cov: 31)
• Consequence: DCDC2 ENST00000378454.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.922+21551C>T		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.922+21551C>T		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.922+21551C>T		intron_variant		1	NM_016356.5	ENSP00000367715	P1

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141780 AN: 152070 Hom.: 66568 Cov.: 31

Gnomad AFR AF: 0.804

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.979

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.932 AC: 141885 AN: 152188 Hom.: 66616 Cov.: 31 AF XY: 0.936 AC XY: 69623 AN XY: 74400

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.988

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.979

Gnomad4 OTH AF: 0.954

Alfa AF: 0.951 Hom.: 8579

Bravo AF: 0.923

Asia WGS AF: 0.989 AC: 3438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.63

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: rs1340698; hg19: chr6-24256726;