6-24175094-CTTTA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016356.5(DCDC2):c.1327-264_1327-261del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,836 control chromosomes in the GnomAD database, including 4,018 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (4018 hom., cov: 30)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.583

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 -10 ACMG points.

• BP6: Variant 6-24175094-CTTTA-C is Benign according to our data. Variant chr6-24175094-CTTTA-C is described in ClinVar as [Benign]. Clinvar id is 1289062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.1327-264_1327-261del		intron_variant		ENST00000378454.8
DCDC2	NM_001195610.2	c.1327-264_1327-261del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.1327-264_1327-261del		intron_variant		1	NM_016356.5	P1
DCDC2	ENST00000378450.6	c.586-264_586-261del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21596 AN: 151718 Hom.: 4017 Cov.: 30

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0839

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.142 AC: 21626 AN: 151836 Hom.: 4018 Cov.: 30 AF XY: 0.137 AC XY: 10182 AN XY: 74234

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.0837

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00360

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0932 Hom.: 294

Bravo AF: 0.163

Asia WGS AF: 0.0290 AC: 100 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs112382215; hg19: chr6-24175322;