rs3789219

Variant names:

• chr6-24174896-T-C
• rs3789219
• NM_016356.5:c.1327-62A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-24174896-T-C
• chr6-24174896-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016356.5(DCDC2):​c.1327-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 998,074 control chromosomes in the GnomAD database, including 24,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3584 hom., cov: 32)
  • Exomes 𝑓: 0.20 (20655 hom.)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.655
• Publications: 4 publications found

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]

DCDC2 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• isolated neonatal sclerosing cholangitis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• nephronophthisis 19

  Inheritance: AR Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Boichis syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 66

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 6-24174896-T-C is Benign according to our data. Variant chr6-24174896-T-C is described in ClinVar as Benign. ClinVar VariationId is 682615.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1327-62A>G		intron_variant	Intron 9 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1327-62A>G		intron_variant	Intron 10 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1327-62A>G		intron_variant	Intron 9 of 9	1	NM_016356.5	ENSP00000367715.3
DCDC2	ENST00000378450.6	c.586-62A>G		intron_variant	Intron 2 of 2	1		ENSP00000367711.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30487 AN: 151882 Hom.: 3581 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.199 AC: 168717 AN: 846076 Hom.: 20655 AF XY: 0.201 AC XY: 87306 AN XY: 434310

African (AFR) AF: 0.191 AC: 3521 AN: 18398

American (AMR) AF: 0.306 AC: 8208 AN: 26852

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 4369 AN: 18140

East Asian (EAS) AF: 0.562 AC: 19520 AN: 34704

South Asian (SAS) AF: 0.284 AC: 12455 AN: 43910

European-Finnish (FIN) AF: 0.170 AC: 7421 AN: 43732

Middle Eastern (MID) AF: 0.177 AC: 758 AN: 4278

European-Non Finnish (NFE) AF: 0.169 AC: 104442 AN: 618394

Other (OTH) AF: 0.213 AC: 8023 AN: 37668

GnomAD4 genome AF: 0.201 AC: 30518 AN: 151998 Hom.: 3584 Cov.: 32 AF XY: 0.205 AC XY: 15249 AN XY: 74296

African (AFR) AF: 0.182 AC: 7542 AN: 41466

American (AMR) AF: 0.231 AC: 3524 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3466

East Asian (EAS) AF: 0.591 AC: 3045 AN: 5152

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4818

European-Finnish (FIN) AF: 0.166 AC: 1746 AN: 10520

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11918 AN: 67990

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.193 Hom.: 5450

Bravo AF: 0.207

Asia WGS AF: 0.406 AC: 1409 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.65
CADD	Benign	7.4
DANN	Benign	0.87
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3789219; hg19: chr6-24175124; COSMIC: COSV65828376;