rs3833459

Variant names:

• chr6-24174451-T-TTACAAA
• rs3833459
• NM_016356.5:c.*278_*279insTTTGTA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016356.5(DCDC2):​c.*278_*279insTTTGTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (10995 hom., cov: 0)
  • Exomes 𝑓: 0.24 (2853 hom.)
• Consequence: DCDC2 NM_016356.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.188
• 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: 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 -10 ACMG points.

• BP6: Variant 6-24174451-T-TTACAAA is Benign according to our data. Variant chr6-24174451-T-TTACAAA is described in ClinVar as Benign. ClinVar VariationId is 1224735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 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.*278_*279insTTTGTA		3_prime_UTR	Exon 10 of 10	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.*278_*279insTTTGTA		3_prime_UTR	Exon 11 of 11	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.*278_*279insTTTGTA		3_prime_UTR	Exon 10 of 10	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000378450.6	TSL:1	c.*278_*279insTTTGTA		3_prime_UTR	Exon 3 of 3	ENSP00000367711.3	Q9UHG0-2
	DCDC2	ENST00000883243.1		c.*278_*279insTTTGTA		3_prime_UTR	Exon 11 of 11	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51151 AN: 151526 Hom.: 10983 Cov.: 0

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.235 AC: 18039 AN: 76622 Hom.: 2853 Cov.: 0 AF XY: 0.232 AC XY: 9294 AN XY: 39998

African (AFR) AF: 0.595 AC: 1637 AN: 2750

American (AMR) AF: 0.309 AC: 1034 AN: 3350

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 747 AN: 3158

East Asian (EAS) AF: 0.537 AC: 3115 AN: 5802

South Asian (SAS) AF: 0.241 AC: 612 AN: 2536

European-Finnish (FIN) AF: 0.143 AC: 459 AN: 3218

Middle Eastern (MID) AF: 0.154 AC: 56 AN: 364

European-Non Finnish (NFE) AF: 0.181 AC: 9086 AN: 50162

Other (OTH) AF: 0.245 AC: 1293 AN: 5282

GnomAD4 genome AF: 0.338 AC: 51215 AN: 151648 Hom.: 10995 Cov.: 0 AF XY: 0.337 AC XY: 24976 AN XY: 74140

African (AFR) AF: 0.603 AC: 24827 AN: 41180

American (AMR) AF: 0.310 AC: 4733 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3466

East Asian (EAS) AF: 0.588 AC: 3009 AN: 5120

South Asian (SAS) AF: 0.293 AC: 1407 AN: 4808

European-Finnish (FIN) AF: 0.168 AC: 1777 AN: 10584

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13776 AN: 67936

Other (OTH) AF: 0.298 AC: 627 AN: 2102

Alfa AF: 0.288 Hom.: 857

Bravo AF: 0.364

Asia WGS AF: 0.425 AC: 1476 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3833459; hg19: chr6-24174679; COSMIC: COSV105320764;