6-24357379-G-A

Position:

• chr6-24357379-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016356.5(DCDC2):​c.293+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 1,468,030 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (75 hom., cov: 32)
  • Exomes 𝑓: 0.023 (467 hom.)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.840

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]

KAAG1 (HGNC:21031): (kidney associated DCDC2 antisense RNA 1)

KAAG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-24357379-G-A is Benign according to our data. Variant chr6-24357379-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 683196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0249 (3781/151958) while in subpopulation AFR AF= 0.0434 (1798/41452). AF 95% confidence interval is 0.0417. There are 75 homozygotes in gnomad4. There are 1705 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 75 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.293+79C>T		intron_variant		ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.293+79C>T		intron_variant			NP_001182539.1
KAAG1	NR_174942.1	n.477G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.293+79C>T		intron_variant		1	NM_016356.5	ENSP00000367715.3
KAAG1	ENST00000274766.2	n.477G>A		non_coding_transcript_exon_variant	1/1	6	NM_181337.4
DCDC2	ENST00000436313.1	c.194+79C>T		intron_variant		3		ENSP00000410939.1

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3777 AN: 151838 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.0434

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0207

GnomAD4 exome AF: 0.0231 AC: 30358 AN: 1316072 Hom.: 467 Cov.: 24 AF XY: 0.0222 AC XY: 14350 AN XY: 645086

Gnomad4 AFR exome AF: 0.0423

Gnomad4 AMR exome AF: 0.00973

Gnomad4 ASJ exome AF: 0.00682

Gnomad4 EAS exome AF: 0.0000523

Gnomad4 SAS exome AF: 0.000276

Gnomad4 FIN exome AF: 0.00507

Gnomad4 NFE exome AF: 0.0265

Gnomad4 OTH exome AF: 0.0208

GnomAD4 genome AF: 0.0249 AC: 3781 AN: 151958 Hom.: 75 Cov.: 32 AF XY: 0.0230 AC XY: 1705 AN XY: 74268

Gnomad4 AFR AF: 0.0434

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00359

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.0244 Hom.: 5

Bravo AF: 0.0270

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.61
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140803474; hg19: chr6-24357607;