chr6-24382669-G-A

Variant names:

• chr6-24382669-G-A
• rs811103
• NM_001195610.2:c.-98+512C>T

Variant summary

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

The NM_001195610.2(DCDC2):​c.-98+512C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,992 control chromosomes in the GnomAD database, including 23,936 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 0.54 (23936 hom., cov: 32)
• Consequence: DCDC2 NM_001195610.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195610.2. 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_001195610.2		c.-98+512C>T		intron	N/A	NP_001182539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81444 AN: 151872 Hom.: 23923 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.536 AC: 81470 AN: 151992 Hom.: 23936 Cov.: 32 AF XY: 0.541 AC XY: 40210 AN XY: 74292

African (AFR) AF: 0.279 AC: 11573 AN: 41432

American (AMR) AF: 0.649 AC: 9914 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2041 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4126 AN: 5164

South Asian (SAS) AF: 0.705 AC: 3399 AN: 4824

European-Finnish (FIN) AF: 0.567 AC: 5991 AN: 10572

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42468 AN: 67946

Other (OTH) AF: 0.547 AC: 1153 AN: 2108

Alfa AF: 0.606 Hom.: 122453

Bravo AF: 0.531

Asia WGS AF: 0.708 AC: 2464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.68
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs811103; hg19: chr6-24382897;