6-24174606-T-A

Variant names:

• chr6-24174606-T-A
• rs7764902
• NM_016356.5:c.*124A>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.*124A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 585,542 control chromosomes in the GnomAD database, including 5,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (4079 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1359 hom.)
• Consequence: DCDC2 NM_016356.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.941
• Publications: 4 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
• autosomal recessive nonsyndromic hearing loss 66

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-24174606-T-A is Benign according to our data. Variant chr6-24174606-T-A is described in ClinVar as Benign. ClinVar VariationId is 1263120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 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.*124A>T		3_prime_UTR	Exon 10 of 10	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.*124A>T		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.*124A>T		3_prime_UTR	Exon 10 of 10	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000378450.6	TSL:1	c.*124A>T		3_prime_UTR	Exon 3 of 3	ENSP00000367711.3	Q9UHG0-2
	DCDC2	ENST00000883243.1		c.*124A>T		3_prime_UTR	Exon 11 of 11	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21689 AN: 152110 Hom.: 4078 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0282

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0363 AC: 15740 AN: 433314 Hom.: 1359 Cov.: 6 AF XY: 0.0333 AC XY: 7580 AN XY: 227554

African (AFR) AF: 0.427 AC: 5112 AN: 11968

American (AMR) AF: 0.0529 AC: 1007 AN: 19028

Ashkenazi Jewish (ASJ) AF: 0.0263 AC: 323 AN: 12288

East Asian (EAS) AF: 0.00 AC: 0 AN: 30922

South Asian (SAS) AF: 0.00141 AC: 37 AN: 26164

European-Finnish (FIN) AF: 0.00390 AC: 124 AN: 31766

Middle Eastern (MID) AF: 0.0320 AC: 73 AN: 2284

European-Non Finnish (NFE) AF: 0.0283 AC: 7792 AN: 274916

Other (OTH) AF: 0.0530 AC: 1272 AN: 23978

GnomAD4 genome AF: 0.143 AC: 21718 AN: 152228 Hom.: 4079 Cov.: 33 AF XY: 0.137 AC XY: 10199 AN XY: 74446

African (AFR) AF: 0.437 AC: 18115 AN: 41468

American (AMR) AF: 0.0824 AC: 1262 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00310 AC: 15 AN: 4832

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10624

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0281 AC: 1913 AN: 68018

Other (OTH) AF: 0.123 AC: 260 AN: 2114

Alfa AF: 0.0894 Hom.: 303

Bravo AF: 0.163

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		-0.94
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: rs7764902; hg19: chr6-24174834;