NM_016356.5:c.705-318A>G

Variant names:

• chr6-24289224-T-C
• rs2296539
• NM_016356.5:c.705-318A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016356.5(DCDC2):​c.705-318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,118 control chromosomes in the GnomAD database, including 25,459 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (25459 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016356.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	NM_016356.5	MANE Select	c.705-318A>G		intron	N/A	NP_057440.2
	DCDC2	NM_001195610.2		c.705-318A>G		intron	N/A	NP_001182539.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.705-318A>G		intron	N/A	ENSP00000367715.3
	DCDC2	ENST00000883243.1		c.705-318A>G		intron	N/A	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79763 AN: 152000 Hom.: 25455 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.524 AC: 79769 AN: 152118 Hom.: 25459 Cov.: 33 AF XY: 0.534 AC XY: 39729 AN XY: 74336

African (AFR) AF: 0.140 AC: 5816 AN: 41528

American (AMR) AF: 0.639 AC: 9767 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2412 AN: 3472

East Asian (EAS) AF: 0.789 AC: 4088 AN: 5178

South Asian (SAS) AF: 0.658 AC: 3171 AN: 4816

European-Finnish (FIN) AF: 0.746 AC: 7873 AN: 10554

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44733 AN: 67964

Other (OTH) AF: 0.541 AC: 1139 AN: 2106

Alfa AF: 0.584 Hom.: 3604

Bravo AF: 0.496

Asia WGS AF: 0.682 AC: 2370 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.40
PhyloP100		0.33
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: rs2296539; hg19: chr6-24289452;