rs1419228

Variant names:

• chr6-24178078-G-A
• rs1419228
• NM_016356.5:c.1326+252C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24178078-G-A
• chr6-24178078-G-C
• chr6-24178078-G-T

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.1326+252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,078 control chromosomes in the GnomAD database, including 43,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (43359 hom., cov: 31)
• Consequence: DCDC2 NM_016356.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.418
• Publications: 20 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=-0.94).
• BP6: Variant 6-24178078-G-A is Benign according to our data. Variant chr6-24178078-G-A is described in ClinVar as Benign. ClinVar VariationId is 1259301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.1326+252C>T		intron_variant	Intron 9 of 9	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.1326+252C>T		intron_variant	Intron 10 of 10		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.1326+252C>T		intron_variant	Intron 9 of 9	1	NM_016356.5	ENSP00000367715.3
DCDC2	ENST00000378450.6	c.585+252C>T		intron_variant	Intron 2 of 2	1		ENSP00000367711.3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111863 AN: 151960 Hom.: 43335 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.736 AC: 111941 AN: 152078 Hom.: 43359 Cov.: 31 AF XY: 0.746 AC XY: 55476 AN XY: 74354

African (AFR) AF: 0.479 AC: 19839 AN: 41412

American (AMR) AF: 0.787 AC: 12019 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2698 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5044 AN: 5184

South Asian (SAS) AF: 0.884 AC: 4272 AN: 4830

European-Finnish (FIN) AF: 0.937 AC: 9935 AN: 10604

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.820 AC: 55733 AN: 67992

Other (OTH) AF: 0.718 AC: 1516 AN: 2110

Alfa AF: 0.793 Hom.: 197902

Bravo AF: 0.711

Asia WGS AF: 0.903 AC: 3137 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 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	-0.94
CADD	Benign	0.54
DANN	Benign	0.18
PhyloP100		-0.42
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: rs1419228; hg19: chr6-24178306; COSMIC: COSV65829942;