rs1419228

Positions:

• chr6-24178078-G-A
• chr6-24178078-G-C
• chr6-24178078-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016356.5(DCDC2):​c.1326+252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,078 control chromosomes in the GnomAD database, including 43,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (43359 hom., cov: 31)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.418

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 6-24178078-G-A is Benign according to our data. Variant chr6-24178078-G-A is described in ClinVar as [Benign]. Clinvar id is 1259301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1326+252C>T		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1326+252C>T		intron_variant			NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1326+252C>T		intron_variant		1	NM_016356.5	ENSP00000367715.3
DCDC2	ENST00000378450.6	c.585+252C>T		intron_variant		1		ENSP00000367711.3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111863 AN: 151960 Hom.: 43335 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.736 AC: 111941 AN: 152078 Hom.: 43359 Cov.: 31 AF XY: 0.746 AC XY: 55476 AN XY: 74354

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.718

Alfa AF: 0.806 Hom.: 93108

Bravo AF: 0.711

Asia WGS AF: 0.903 AC: 3137 AN: 3476

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 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.54
DANN	Benign	0.18

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: rs1419228; hg19: chr6-24178306; COSMIC: COSV65829942;