rs807701

Variant names:

• chr6-24273563-G-A
• rs807701
• NM_016356.5:c.922+4486C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24273563-G-A
• chr6-24273563-G-C
• chr6-24273563-G-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.922+4486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,150 control chromosomes in the GnomAD database, including 26,289 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 0.56 (26289 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 34 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	NM_016356.5	MANE Select	c.922+4486C>T		intron	N/A	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.922+4486C>T		intron	N/A	NP_001182539.1	Q9UHG0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.922+4486C>T		intron	N/A	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000883243.1		c.922+4486C>T		intron	N/A	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84444 AN: 152032 Hom.: 26274 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.555 AC: 84490 AN: 152150 Hom.: 26289 Cov.: 33 AF XY: 0.564 AC XY: 41967 AN XY: 74392

African (AFR) AF: 0.253 AC: 10518 AN: 41494

American (AMR) AF: 0.650 AC: 9946 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3470

East Asian (EAS) AF: 0.785 AC: 4051 AN: 5162

South Asian (SAS) AF: 0.657 AC: 3170 AN: 4822

European-Finnish (FIN) AF: 0.737 AC: 7804 AN: 10596

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44654 AN: 67986

Other (OTH) AF: 0.557 AC: 1177 AN: 2112

Alfa AF: 0.613 Hom.: 34648

Bravo AF: 0.532

Asia WGS AF: 0.682 AC: 2376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.1
DANN	Benign	0.72
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs807701; hg19: chr6-24273791;