6-24369287-T-C

Variant names:

• chr6-24369287-T-C
• rs793663
• NM_001195610.2:c.-97-11440A>G

Variant summary

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

The NM_001195610.2(DCDC2):​c.-97-11440A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,902 control chromosomes in the GnomAD database, including 24,405 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 (24405 hom., cov: 31)
• Consequence: DCDC2 NM_001195610.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_001195610.2	c.-97-11440A>G		intron_variant	Intron 1 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82818 AN: 151786 Hom.: 24387 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.545 AC: 82851 AN: 151902 Hom.: 24405 Cov.: 31 AF XY: 0.551 AC XY: 40872 AN XY: 74242

African (AFR) AF: 0.311 AC: 12878 AN: 41414

American (AMR) AF: 0.654 AC: 9992 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2039 AN: 3470

East Asian (EAS) AF: 0.799 AC: 4118 AN: 5154

South Asian (SAS) AF: 0.705 AC: 3393 AN: 4816

European-Finnish (FIN) AF: 0.566 AC: 5964 AN: 10534

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42493 AN: 67932

Other (OTH) AF: 0.555 AC: 1169 AN: 2108

Alfa AF: 0.560 Hom.: 3120

Bravo AF: 0.541

Asia WGS AF: 0.710 AC: 2469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.66
PhyloP100		0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs793663; hg19: chr6-24369515;