6-24234705-A-G

Variant names:

• chr6-24234705-A-G
• rs793834
• NM_016356.5:c.923-29603T>C

Variant summary

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

The NM_016356.5(DCDC2):​c.923-29603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 152,068 control chromosomes in the GnomAD database, including 33,311 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 0.63 (33311 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.751 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.923-29603T>C		intron	N/A	NP_057440.2
	DCDC2	NM_001195610.2		c.923-29603T>C		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.923-29603T>C		intron	N/A	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.634 AC: 96372 AN: 151950 Hom.: 33307 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.634 AC: 96401 AN: 152068 Hom.: 33311 Cov.: 32 AF XY: 0.641 AC XY: 47608 AN XY: 74328

African (AFR) AF: 0.334 AC: 13840 AN: 41476

American (AMR) AF: 0.718 AC: 10973 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2402 AN: 3468

East Asian (EAS) AF: 0.603 AC: 3109 AN: 5156

South Asian (SAS) AF: 0.741 AC: 3571 AN: 4820

European-Finnish (FIN) AF: 0.840 AC: 8872 AN: 10560

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51419 AN: 67986

Other (OTH) AF: 0.655 AC: 1380 AN: 2108

Alfa AF: 0.712 Hom.: 135868

Bravo AF: 0.607

Asia WGS AF: 0.649 AC: 2259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.88
DANN	Benign	0.51
PhyloP100		-0.076
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: rs793834; hg19: chr6-24234933;