rs33943110

chr6-24357568-G-Achr6-24357568-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_016356.5(DCDC2):c.183C>T(p.Ala61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,613,326 control chromosomes in the GnomAD database, including 2,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (198 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2410 hom.)
• Consequence: DCDC2 NM_016356.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.41

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)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 6-24357568-G-A is Benign according to our data. Variant chr6-24357568-G-A is described in ClinVar as [Benign]. Clinvar id is 466323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.183C>T	p.Ala61=	synonymous_variant	1/10	ENST00000378454.8
KAAG1	NR_174942.1	n.666G>A		non_coding_transcript_exon_variant	1/1
DCDC2	NM_001195610.2	c.183C>T	p.Ala61=	synonymous_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.183C>T	p.Ala61=	synonymous_variant	1/10	1	NM_016356.5	P1
KAAG1	ENST00000274766.2	n.666G>A		non_coding_transcript_exon_variant	1/1
DCDC2	ENST00000436313.1	c.87C>T	p.Ala29=	synonymous_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6625 AN: 152030 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.00503

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0523

GnomAD3 exomes AF: 0.0471 AC: 11665 AN: 247886 Hom.: 384 AF XY: 0.0489 AC XY: 6577 AN XY: 134580

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.0330

Gnomad ASJ exome AF: 0.0712

Gnomad EAS exome AF: 0.00223

Gnomad SAS exome AF: 0.0535

Gnomad FIN exome AF: 0.0336

Gnomad NFE exome AF: 0.0622

Gnomad OTH exome AF: 0.0540

GnomAD4 exome AF: 0.0547 AC: 79963 AN: 1461178 Hom.: 2410 Cov.: 31 AF XY: 0.0549 AC XY: 39873 AN XY: 726898

Gnomad4 AFR exome AF: 0.0120

Gnomad4 AMR exome AF: 0.0346

Gnomad4 ASJ exome AF: 0.0706

Gnomad4 EAS exome AF: 0.00212

Gnomad4 SAS exome AF: 0.0522

Gnomad4 FIN exome AF: 0.0350

Gnomad4 NFE exome AF: 0.0593

Gnomad4 OTH exome AF: 0.0562

GnomAD4 genome AF: 0.0436 AC: 6628 AN: 152148 Hom.: 198 Cov.: 32 AF XY: 0.0417 AC XY: 3104 AN XY: 74412

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0697

Gnomad4 EAS AF: 0.00504

Gnomad4 SAS AF: 0.0530

Gnomad4 FIN AF: 0.0269

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0488 Hom.: 130

Bravo AF: 0.0428

Asia WGS AF: 0.0340 AC: 117 AN: 3478

EpiCase AF: 0.0692

EpiControl AF: 0.0686

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2017

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. -

Autosomal recessive nonsyndromic hearing loss 66;C4479344:Isolated neonatal sclerosing cholangitis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	5.3
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs33943110; hg19: chr6-24357796;