rs34705735

chr6-24206867-G-C

Variant summary

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

The NM_016356.5(DCDC2):c.923-1765C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 152,238 control chromosomes in the GnomAD database, including 19 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 0.011 (19 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.88).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0111 (1695/152238) while in subpopulation EAS AF= 0.039 (202/5182). AF 95% confidence interval is 0.0346. There are 19 homozygotes in gnomad4. There are 865 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.923-1765C>G		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.923-1765C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.923-1765C>G		intron_variant		1	NM_016356.5	P1

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1695 AN: 152120 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00270

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.0393

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.00766

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

GnomAD4 genome AF: 0.0111 AC: 1695 AN: 152238 Hom.: 19 Cov.: 32 AF XY: 0.0116 AC XY: 865 AN XY: 74434

Gnomad4 AFR AF: 0.00269

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.0104 Hom.: 2

Bravo AF: 0.0102

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.58
Dann	Benign	0.33

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: rs34705735; hg19: chr6-24207095;