chr6-24191231-G-T

Variant names:

• chr6-24191231-G-T
• rs2027584
• NM_016356.5:c.1024-12599C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016356.5(DCDC2):​c.1024-12599C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,220 control chromosomes in the GnomAD database, including 1,141 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 0.11 (1141 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.53
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1024-12599C>A		intron_variant	Intron 8 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1024-12599C>A		intron_variant	Intron 9 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1024-12599C>A		intron_variant	Intron 8 of 9	1	NM_016356.5	ENSP00000367715.3
DCDC2	ENST00000378450.6	c.283-12599C>A		intron_variant	Intron 1 of 2	1		ENSP00000367711.3

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16355 AN: 152102 Hom.: 1143 Cov.: 33

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0913

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

GnomAD4 genome AF: 0.107 AC: 16361 AN: 152220 Hom.: 1141 Cov.: 33 AF XY: 0.111 AC XY: 8269 AN XY: 74404

African (AFR) AF: 0.0564 AC: 2343 AN: 41552

American (AMR) AF: 0.0961 AC: 1469 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 642 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1877 AN: 5178

South Asian (SAS) AF: 0.152 AC: 731 AN: 4816

European-Finnish (FIN) AF: 0.117 AC: 1240 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7799 AN: 68002

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.111 Hom.: 2143

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.022
DANN	Benign	0.37
PhyloP100		-3.5
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: rs2027584; hg19: chr6-24191459;