NM_016356.5:c.1023+1506A>C

Variant names:

• chr6-24203496-T-G
• rs1087294
• NM_016356.5:c.1023+1506A>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.1023+1506A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 151,986 control chromosomes in the GnomAD database, including 30,519 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 0.62 (30519 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 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.1023+1506A>C		intron	N/A	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.1023+1506A>C		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.1023+1506A>C		intron	N/A	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000378450.6	TSL:1	c.282+1506A>C		intron	N/A	ENSP00000367711.3	Q9UHG0-2
	DCDC2	ENST00000883243.1		c.1023+1506A>C		intron	N/A	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94281 AN: 151868 Hom.: 30507 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.621 AC: 94327 AN: 151986 Hom.: 30519 Cov.: 32 AF XY: 0.626 AC XY: 46488 AN XY: 74310

African (AFR) AF: 0.427 AC: 17673 AN: 41404

American (AMR) AF: 0.689 AC: 10520 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2051 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3054 AN: 5160

South Asian (SAS) AF: 0.652 AC: 3140 AN: 4814

European-Finnish (FIN) AF: 0.813 AC: 8603 AN: 10578

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.694 AC: 47167 AN: 67970

Other (OTH) AF: 0.627 AC: 1324 AN: 2110

Alfa AF: 0.635 Hom.: 3764

Bravo AF: 0.600

Asia WGS AF: 0.613 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		0.29
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: rs1087294; hg19: chr6-24203724;