rs143313706

chr6-24178612-G-Achr6-24178612-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_016356.5(DCDC2):c.1044C>T(p.Asp348=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,612,918 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (29 hom.)
• Consequence: DCDC2 NM_016356.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.237

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 6-24178612-G-A is Benign according to our data. Variant chr6-24178612-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 466321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24178612-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.237 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0029 (441/152016) while in subpopulation AMR AF= 0.00399 (61/15270). AF 95% confidence interval is 0.00319. There are 4 homozygotes in gnomad4. There are 220 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.1044C>T	p.Asp348=	synonymous_variant	9/10	ENST00000378454.8
DCDC2	NM_001195610.2	c.1044C>T	p.Asp348=	synonymous_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.1044C>T	p.Asp348=	synonymous_variant	9/10	1	NM_016356.5	P1
DCDC2	ENST00000378450.6	c.303C>T	p.Asp101=	synonymous_variant	2/3	1

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 151898 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00391 AC: 980 AN: 250470 Hom.: 7 AF XY: 0.00414 AC XY: 560 AN XY: 135386

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.00109

Gnomad SAS exome AF: 0.00400

Gnomad FIN exome AF: 0.000377

Gnomad NFE exome AF: 0.00382

Gnomad OTH exome AF: 0.00393

GnomAD4 exome AF: 0.00315 AC: 4603 AN: 1460902 Hom.: 29 Cov.: 32 AF XY: 0.00329 AC XY: 2390 AN XY: 726752

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00253

Gnomad4 ASJ exome AF: 0.0285

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.00407

Gnomad4 FIN exome AF: 0.000170

Gnomad4 NFE exome AF: 0.00273

Gnomad4 OTH exome AF: 0.00444

GnomAD4 genome AF: 0.00290 AC: 441 AN: 152016 Hom.: 4 Cov.: 32 AF XY: 0.00296 AC XY: 220 AN XY: 74266

Gnomad4 AFR AF: 0.000724

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.000968

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00316

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00514 Hom.: 1

Bravo AF: 0.00319

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00534

EpiControl AF: 0.00557

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 01, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Aug 24, 2020	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	DCDC2: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

Autosomal recessive nonsyndromic hearing loss 66;C4015542:Nephronophthisis 19;C4479344:Isolated neonatal sclerosing cholangitis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Nov 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	7.9
Dann	Benign	0.39

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: rs143313706; hg19: chr6-24178840; COSMIC: COSV65828641;