rs6922023

Variant names:

• chr6-24347889-G-A
• rs6922023
• NM_016356.5:c.348+5680C>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.348+5680C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,034 control chromosomes in the GnomAD database, including 4,283 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 0.22 (4283 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 14 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	NM_016356.5	MANE Select	c.348+5680C>T		intron	N/A	NP_057440.2
	DCDC2	NM_001195610.2		c.348+5680C>T		intron	N/A	NP_001182539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.348+5680C>T		intron	N/A	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33913 AN: 151916 Hom.: 4272 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.223 AC: 33954 AN: 152034 Hom.: 4283 Cov.: 32 AF XY: 0.225 AC XY: 16743 AN XY: 74320

African (AFR) AF: 0.349 AC: 14438 AN: 41422

American (AMR) AF: 0.177 AC: 2713 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 588 AN: 3464

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5168

South Asian (SAS) AF: 0.202 AC: 972 AN: 4822

European-Finnish (FIN) AF: 0.158 AC: 1669 AN: 10570

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11338 AN: 67984

Other (OTH) AF: 0.187 AC: 395 AN: 2112

Alfa AF: 0.185 Hom.: 2409

Bravo AF: 0.228

Asia WGS AF: 0.282 AC: 979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.58
PhyloP100		-0.0020
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: rs6922023; hg19: chr6-24348117;