chr6-24233060-G-A

Variant names:

• chr6-24233060-G-A
• rs9460980
• NM_016356.5:c.923-27958C>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.923-27958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,032 control chromosomes in the GnomAD database, including 22,022 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 (22022 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.923-27958C>T		intron_variant	Intron 7 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.923-27958C>T		intron_variant	Intron 8 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.923-27958C>T		intron_variant	Intron 7 of 9	1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78378 AN: 151914 Hom.: 22018 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.516 AC: 78397 AN: 152032 Hom.: 22022 Cov.: 32 AF XY: 0.519 AC XY: 38593 AN XY: 74326

African (AFR) AF: 0.280 AC: 11581 AN: 41418

American (AMR) AF: 0.604 AC: 9239 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2217 AN: 5164

South Asian (SAS) AF: 0.554 AC: 2666 AN: 4816

European-Finnish (FIN) AF: 0.663 AC: 7015 AN: 10576

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41663 AN: 67984

Other (OTH) AF: 0.542 AC: 1144 AN: 2112

Alfa AF: 0.588 Hom.: 16626

Bravo AF: 0.497

Asia WGS AF: 0.472 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		-0.19
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: rs9460980; hg19: chr6-24233288;