6-24180138-A-G

Variant names:

• chr6-24180138-A-G
• rs2996452
• NM_016356.5:c.1024-1506T>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.1024-1506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 151,948 control chromosomes in the GnomAD database, including 55,832 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 0.86 (55832 hom., cov: 28)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 2 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 (AMR) allele frequency at 95% confidence interval = 0.87 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.1024-1506T>C		intron	N/A	NP_057440.2
	DCDC2	NM_001195610.2		c.1024-1506T>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.1024-1506T>C		intron	N/A	ENSP00000367715.3
	DCDC2	ENST00000378450.6	TSL:1	c.283-1506T>C		intron	N/A	ENSP00000367711.3

Frequencies

GnomAD3 genomes AF: 0.856 AC: 129956 AN: 151830 Hom.: 55785 Cov.: 28

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.856 AC: 130065 AN: 151948 Hom.: 55832 Cov.: 28 AF XY: 0.855 AC XY: 63458 AN XY: 74258

African (AFR) AF: 0.872 AC: 36119 AN: 41424

American (AMR) AF: 0.883 AC: 13486 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2713 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3258 AN: 5154

South Asian (SAS) AF: 0.819 AC: 3940 AN: 4810

European-Finnish (FIN) AF: 0.879 AC: 9256 AN: 10534

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58329 AN: 67956

Other (OTH) AF: 0.870 AC: 1840 AN: 2114

Alfa AF: 0.848 Hom.: 31669

Bravo AF: 0.854

Asia WGS AF: 0.760 AC: 2644 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	3.1
DANN	Benign	0.54
PhyloP100		0.055
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: rs2996452; hg19: chr6-24180366;