6-24272156-C-A

Variant names:

• chr6-24272156-C-A
• rs2792682
• NM_016356.5:c.922+5893G>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.922+5893G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,092 control chromosomes in the GnomAD database, including 40,247 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 0.71 (40247 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.922+5893G>T		intron_variant	Intron 7 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.922+5893G>T		intron_variant	Intron 8 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.922+5893G>T		intron_variant	Intron 7 of 9	1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108238 AN: 151974 Hom.: 40233 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.712 AC: 108294 AN: 152092 Hom.: 40247 Cov.: 32 AF XY: 0.720 AC XY: 53571 AN XY: 74364

African (AFR) AF: 0.487 AC: 20193 AN: 41430

American (AMR) AF: 0.773 AC: 11815 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2628 AN: 3470

East Asian (EAS) AF: 0.951 AC: 4926 AN: 5178

South Asian (SAS) AF: 0.793 AC: 3823 AN: 4818

European-Finnish (FIN) AF: 0.895 AC: 9489 AN: 10598

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.781 AC: 53095 AN: 67996

Other (OTH) AF: 0.697 AC: 1469 AN: 2108

Alfa AF: 0.750 Hom.: 124997

Bravo AF: 0.691

Asia WGS AF: 0.844 AC: 2937 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.62
PhyloP100		0.077
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: rs2792682; hg19: chr6-24272384;