rs807709

Variant names:

• chr6-24297075-G-A
• rs807709
• NM_016356.5:c.557+4640C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24297075-G-A
• chr6-24297075-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.557+4640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,228 control chromosomes in the GnomAD database, including 51,014 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 0.81 (51014 hom., cov: 32)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.557+4640C>T		intron_variant	Intron 4 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.557+4640C>T		intron_variant	Intron 5 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.557+4640C>T		intron_variant	Intron 4 of 9	1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123703 AN: 152110 Hom.: 50998 Cov.: 32

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.813 AC: 123765 AN: 152228 Hom.: 51014 Cov.: 32 AF XY: 0.818 AC XY: 60918 AN XY: 74440

African (AFR) AF: 0.671 AC: 27821 AN: 41490

American (AMR) AF: 0.860 AC: 13150 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2821 AN: 3472

East Asian (EAS) AF: 0.949 AC: 4923 AN: 5190

South Asian (SAS) AF: 0.814 AC: 3928 AN: 4828

European-Finnish (FIN) AF: 0.938 AC: 9952 AN: 10612

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58621 AN: 68022

Other (OTH) AF: 0.791 AC: 1670 AN: 2110

Alfa AF: 0.831 Hom.: 6583

Bravo AF: 0.801

Asia WGS AF: 0.866 AC: 3014 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	0.082
DANN	Benign	0.20
PhyloP100		-1.5
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: rs807709; hg19: chr6-24297303;