rs7747779

Positions:

• chr6-24223379-C-A
• chr6-24223379-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016356.5(DCDC2):​c.923-18277G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 152,188 control chromosomes in the GnomAD database, including 16 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 0.014 (16 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948

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=-0.87).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0144 (2195/152188) while in subpopulation SAS AF= 0.0239 (115/4820). AF 95% confidence interval is 0.0204. There are 16 homozygotes in gnomad4. There are 1073 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.923-18277G>T		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.923-18277G>T		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.923-18277G>T		intron_variant		1	NM_016356.5	ENSP00000367715	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2197 AN: 152070 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00317

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152188 Hom.: 16 Cov.: 32 AF XY: 0.0144 AC XY: 1073 AN XY: 74396

Gnomad4 AFR AF: 0.00316

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0239

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0106 Hom.: 2047

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.53

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: rs7747779; hg19: chr6-24223607;