6-24174575-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016356.5(DCDC2):c.*155T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 480,054 control chromosomes in the GnomAD database, including 5,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (4085 hom., cov: 33)
  • Exomes 𝑓: 0.035 (1037 hom.)
• Consequence: DCDC2 NM_016356.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.434

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-24174575-A-C is Benign according to our data. Variant chr6-24174575-A-C is described in ClinVar as [Benign]. Clinvar id is 1241943.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.*155T>G		3_prime_UTR_variant	10/10	ENST00000378454.8
DCDC2	NM_001195610.2	c.*155T>G		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.*155T>G		3_prime_UTR_variant	10/10	1	NM_016356.5	P1
DCDC2	ENST00000378450.6	c.*155T>G		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21730 AN: 152106 Hom.: 4084 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.124

GnomAD4 exome AF: 0.0350 AC: 11483 AN: 327830 Hom.: 1037 Cov.: 5 AF XY: 0.0324 AC XY: 5546 AN XY: 171156

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.0550

Gnomad4 ASJ exome AF: 0.0267

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00147

Gnomad4 FIN exome AF: 0.00386

Gnomad4 NFE exome AF: 0.0257

Gnomad4 OTH exome AF: 0.0546

GnomAD4 genome AF: 0.143 AC: 21759 AN: 152224 Hom.: 4085 Cov.: 33 AF XY: 0.137 AC XY: 10224 AN XY: 74452

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0421 Hom.: 774

Bravo AF: 0.163

Asia WGS AF: 0.0280 AC: 99 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.4
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs7744665; hg19: chr6-24174803;