chr6-24224448-A-G

Variant names:

• chr6-24224448-A-G
• rs707885
• NM_016356.5:c.923-19346T>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.923-19346T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,164 control chromosomes in the GnomAD database, including 55,773 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 0.85 (55773 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.923-19346T>C		intron_variant	Intron 7 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.923-19346T>C		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.923-19346T>C		intron_variant	Intron 7 of 9	1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129528 AN: 152046 Hom.: 55739 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.852 AC: 129620 AN: 152164 Hom.: 55773 Cov.: 32 AF XY: 0.851 AC XY: 63308 AN XY: 74380

African (AFR) AF: 0.739 AC: 30661 AN: 41482

American (AMR) AF: 0.878 AC: 13430 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.904 AC: 3140 AN: 3472

East Asian (EAS) AF: 0.643 AC: 3319 AN: 5162

South Asian (SAS) AF: 0.863 AC: 4156 AN: 4814

European-Finnish (FIN) AF: 0.919 AC: 9736 AN: 10598

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62177 AN: 68020

Other (OTH) AF: 0.881 AC: 1859 AN: 2110

Alfa AF: 0.844 Hom.: 3138

Bravo AF: 0.842

Asia WGS AF: 0.757 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.71
PhyloP100		-1.4
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: rs707885; hg19: chr6-24224676;