chr6-24325399-G-T

Variant names:

• chr6-24325399-G-T
• rs1417740
• NM_016356.5:c.349-23355C>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.349-23355C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 148,754 control chromosomes in the GnomAD database, including 25,336 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 0.53 (25336 hom., cov: 30)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016356.5. 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_016356.5	MANE Select	c.349-23355C>A		intron	N/A	NP_057440.2
	DCDC2	NM_001195610.2		c.349-23355C>A		intron	N/A	NP_001182539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.349-23355C>A		intron	N/A	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.534 AC: 79323 AN: 148644 Hom.: 25339 Cov.: 30

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.533 AC: 79320 AN: 148754 Hom.: 25336 Cov.: 30 AF XY: 0.539 AC XY: 39030 AN XY: 72390

African (AFR) AF: 0.268 AC: 11060 AN: 41292

American (AMR) AF: 0.637 AC: 9517 AN: 14934

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 2392 AN: 3406

East Asian (EAS) AF: 0.693 AC: 2996 AN: 4324

South Asian (SAS) AF: 0.599 AC: 2642 AN: 4408

European-Finnish (FIN) AF: 0.694 AC: 7077 AN: 10202

Middle Eastern (MID) AF: 0.605 AC: 173 AN: 286

European-Non Finnish (NFE) AF: 0.623 AC: 41723 AN: 66924

Other (OTH) AF: 0.543 AC: 1125 AN: 2072

Alfa AF: 0.580 Hom.: 6852

Asia WGS AF: 0.621 AC: 1984 AN: 3190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		0.61
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: rs1417740; hg19: chr6-24325627;