rs1770461

Variant names:

• chr6-24221577-T-A
• rs1770461
• NM_016356.5:c.923-16475A>T

Variant summary

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

The NM_016356.5(DCDC2):​c.923-16475A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,182 control chromosomes in the GnomAD database, including 51,490 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 0.82 (51490 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• 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: Orphanet, Labcorp Genetics (formerly Invitae)
• nephronophthisis 19

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 66

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.886 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.923-16475A>T		intron	N/A	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.923-16475A>T		intron	N/A	NP_001182539.1	Q9UHG0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.923-16475A>T		intron	N/A	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000883243.1		c.923-16475A>T		intron	N/A	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124141 AN: 152064 Hom.: 51478 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.816 AC: 124206 AN: 152182 Hom.: 51490 Cov.: 33 AF XY: 0.815 AC XY: 60664 AN XY: 74396

African (AFR) AF: 0.668 AC: 27699 AN: 41464

American (AMR) AF: 0.854 AC: 13059 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3071 AN: 3472

East Asian (EAS) AF: 0.636 AC: 3286 AN: 5166

South Asian (SAS) AF: 0.811 AC: 3918 AN: 4830

European-Finnish (FIN) AF: 0.904 AC: 9600 AN: 10614

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.892 AC: 60666 AN: 68030

Other (OTH) AF: 0.847 AC: 1788 AN: 2112

Alfa AF: 0.844 Hom.: 6813

Bravo AF: 0.805

Asia WGS AF: 0.721 AC: 2511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.68
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1770461; hg19: chr6-24221805;