rs793720

Variant names:

• chr6-24353052-G-A
• rs793720
• NM_016356.5:c.348+517C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24353052-G-A
• chr6-24353052-G-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.348+517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,110 control chromosomes in the GnomAD database, including 25,358 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 0.55 (25358 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 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+517C>T		intron	N/A	NP_057440.2
	DCDC2	NM_001195610.2		c.348+517C>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+517C>T		intron	N/A	ENSP00000367715.3
	DCDC2	ENST00000436313.1	TSL:3	c.*253C>T		downstream_gene	N/A	ENSP00000410939.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84101 AN: 151994 Hom.: 25343 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.553 AC: 84129 AN: 152110 Hom.: 25358 Cov.: 33 AF XY: 0.558 AC XY: 41509 AN XY: 74354

African (AFR) AF: 0.294 AC: 12216 AN: 41490

American (AMR) AF: 0.672 AC: 10276 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2097 AN: 3468

East Asian (EAS) AF: 0.801 AC: 4148 AN: 5178

South Asian (SAS) AF: 0.706 AC: 3402 AN: 4818

European-Finnish (FIN) AF: 0.581 AC: 6137 AN: 10562

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.645 AC: 43847 AN: 67988

Other (OTH) AF: 0.568 AC: 1199 AN: 2110

Alfa AF: 0.612 Hom.: 7943

Bravo AF: 0.548

Asia WGS AF: 0.710 AC: 2471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.2
DANN	Benign	0.66
PhyloP100		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs793720; hg19: chr6-24353280;