6-24353817-T-C

Variant names:

• chr6-24353817-T-C
• rs3765502
• NM_016356.5:c.294-194A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016356.5(DCDC2):​c.294-194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,262 control chromosomes in the GnomAD database, including 1,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (1342 hom., cov: 33)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110
• Publications: 14 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-24353817-T-C is Benign according to our data. Variant chr6-24353817-T-C is described in ClinVar as Benign. ClinVar VariationId is 1243401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.294-194A>G		intron_variant	Intron 1 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.294-194A>G		intron_variant	Intron 2 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.294-194A>G		intron_variant	Intron 1 of 9	1	NM_016356.5	ENSP00000367715.3
DCDC2	ENST00000436313.1	c.195-194A>G		intron_variant	Intron 1 of 2	3		ENSP00000410939.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15829 AN: 152144 Hom.: 1332 Cov.: 33

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0994

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

GnomAD4 genome AF: 0.104 AC: 15858 AN: 152262 Hom.: 1342 Cov.: 33 AF XY: 0.108 AC XY: 8069 AN XY: 74448

African (AFR) AF: 0.0231 AC: 962 AN: 41568

American (AMR) AF: 0.189 AC: 2891 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3472

East Asian (EAS) AF: 0.394 AC: 2041 AN: 5180

South Asian (SAS) AF: 0.232 AC: 1122 AN: 4828

European-Finnish (FIN) AF: 0.0871 AC: 924 AN: 10604

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7389 AN: 68006

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.110 Hom.: 3683

Bravo AF: 0.108

Asia WGS AF: 0.288 AC: 997 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.81
PhyloP100		-0.011
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: rs3765502; hg19: chr6-24354045;