NM_001195610.2:c.-98+7859C>T

Variant names:

• chr6-24375322-G-A
• rs793694
• NM_001195610.2:c.-98+7859C>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+7859C>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 151,732 control chromosomes in the GnomAD database, including 23,901 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 (23901 hom., cov: 29)
• Consequence: DCDC2 NM_001195610.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887
• Publications: 0 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: Orphanet, Labcorp Genetics (formerly Invitae)
• nephronophthisis 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Boichis syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 66

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	NM_001195610.2		c.-98+7859C>T		intron	N/A	NP_001182539.1	Q9UHG0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81284 AN: 151612 Hom.: 23887 Cov.: 29

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.536 AC: 81310 AN: 151732 Hom.: 23901 Cov.: 29 AF XY: 0.541 AC XY: 40110 AN XY: 74118

African (AFR) AF: 0.279 AC: 11543 AN: 41334

American (AMR) AF: 0.649 AC: 9904 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2037 AN: 3464

East Asian (EAS) AF: 0.800 AC: 4103 AN: 5128

South Asian (SAS) AF: 0.704 AC: 3376 AN: 4794

European-Finnish (FIN) AF: 0.567 AC: 5974 AN: 10544

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.625 AC: 42416 AN: 67894

Other (OTH) AF: 0.548 AC: 1154 AN: 2104

Alfa AF: 0.553 Hom.: 3091

Bravo AF: 0.531

Asia WGS AF: 0.710 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs793694; hg19: chr6-24375550;