rs7747779

Variant names:

• chr6-24223379-C-A
• rs7747779
• NM_016356.5:c.923-18277G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24223379-C-A
• chr6-24223379-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016356.5(DCDC2):​c.923-18277G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 152,188 control chromosomes in the GnomAD database, including 16 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 0.014 (16 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.948
• Publications: 1 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).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0144 (2195/152188) while in subpopulation SAS AF = 0.0239 (115/4820). AF 95% confidence interval is 0.0204. There are 16 homozygotes in GnomAd4. There are 1073 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.923-18277G>T		intron_variant	Intron 7 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.923-18277G>T		intron_variant	Intron 8 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.923-18277G>T		intron_variant	Intron 7 of 9	1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2197 AN: 152070 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00317

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152188 Hom.: 16 Cov.: 32 AF XY: 0.0144 AC XY: 1073 AN XY: 74396

African (AFR) AF: 0.00316 AC: 131 AN: 41498

American (AMR) AF: 0.0141 AC: 215 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5178

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4820

European-Finnish (FIN) AF: 0.0137 AC: 145 AN: 10582

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1447 AN: 68030

Other (OTH) AF: 0.0171 AC: 36 AN: 2110

Alfa AF: 0.0106 Hom.: 2047

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.53
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism

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: rs7747779; hg19: chr6-24223607;