chr6-24336788-C-A

Variant names:

• chr6-24336788-C-A
• rs6456605
• NM_016356.5:c.348+16781G>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+16781G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 151,682 control chromosomes in the GnomAD database, including 9,586 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 0.32 (9586 hom., cov: 31)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• 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: 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 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.348+16781G>T		intron	N/A	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.348+16781G>T		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.348+16781G>T		intron	N/A	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000883243.1		c.348+16781G>T		intron	N/A	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49136 AN: 151566 Hom.: 9570 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.324 AC: 49197 AN: 151682 Hom.: 9586 Cov.: 31 AF XY: 0.318 AC XY: 23592 AN XY: 74106

African (AFR) AF: 0.552 AC: 22806 AN: 41280

American (AMR) AF: 0.267 AC: 4071 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1038 AN: 5180

South Asian (SAS) AF: 0.198 AC: 955 AN: 4814

European-Finnish (FIN) AF: 0.190 AC: 1998 AN: 10504

Middle Eastern (MID) AF: 0.245 AC: 71 AN: 290

European-Non Finnish (NFE) AF: 0.246 AC: 16735 AN: 67904

Other (OTH) AF: 0.318 AC: 672 AN: 2110

Alfa AF: 0.278 Hom.: 1367

Bravo AF: 0.342

Asia WGS AF: 0.206 AC: 715 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.30
PhyloP100		0.089
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: rs6456605; hg19: chr6-24337016;