rs1087291

Variant names:

• chr6-24200181-A-G
• rs1087291
• NM_016356.5:c.1023+4821T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-24200181-A-G
• chr6-24200181-A-T

Variant summary

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

The NM_016356.5(DCDC2):​c.1023+4821T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,038 control chromosomes in the GnomAD database, including 18,716 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 0.45 (18716 hom., cov: 31)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1023+4821T>C		intron_variant	Intron 8 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1023+4821T>C		intron_variant	Intron 9 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1023+4821T>C		intron_variant	Intron 8 of 9	1	NM_016356.5	ENSP00000367715.3
DCDC2	ENST00000378450.6	c.282+4821T>C		intron_variant	Intron 1 of 2	1		ENSP00000367711.3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68430 AN: 151920 Hom.: 18714 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.450 AC: 68437 AN: 152038 Hom.: 18716 Cov.: 31 AF XY: 0.456 AC XY: 33917 AN XY: 74314

African (AFR) AF: 0.128 AC: 5332 AN: 41510

American (AMR) AF: 0.532 AC: 8133 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2105 AN: 5148

South Asian (SAS) AF: 0.494 AC: 2379 AN: 4814

European-Finnish (FIN) AF: 0.666 AC: 7036 AN: 10560

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39978 AN: 67946

Other (OTH) AF: 0.455 AC: 959 AN: 2108

Alfa AF: 0.500 Hom.: 2576

Bravo AF: 0.423

Asia WGS AF: 0.423 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1087291; hg19: chr6-24200409;