6-24174446-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016356.5(DCDC2):c.*284T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 191,432 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0066 (5 hom.)
• Consequence: DCDC2 NM_016356.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500

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=-0.74).
• BP6: Variant 6-24174446-A-G is Benign according to our data. Variant chr6-24174446-A-G is described in ClinVar as [Benign]. Clinvar id is 1250200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0162 (2076/128292) while in subpopulation AFR AF= 0.0514 (1380/26874). AF 95% confidence interval is 0.0491. There are 28 homozygotes in gnomad4. There are 947 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC2	NM_016356.5	c.*284T>C		3_prime_UTR_variant	10/10	ENST00000378454.8
DCDC2	NM_001195610.2	c.*284T>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC2	ENST00000378454.8	c.*284T>C		3_prime_UTR_variant	10/10	1	NM_016356.5	P1
DCDC2	ENST00000378450.6	c.*284T>C		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2076 AN: 128198 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.000312

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000300

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00668

Gnomad OTH AF: 0.0174

GnomAD4 exome AF: 0.00656 AC: 414 AN: 63140 Hom.: 5 Cov.: 0 AF XY: 0.00633 AC XY: 211 AN XY: 33330

Gnomad4 AFR exome AF: 0.0371

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000363

Gnomad4 NFE exome AF: 0.00655

Gnomad4 OTH exome AF: 0.00806

GnomAD4 genome AF: 0.0162 AC: 2076 AN: 128292 Hom.: 28 Cov.: 33 AF XY: 0.0152 AC XY: 947 AN XY: 62472

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.0173

Gnomad4 ASJ AF: 0.000312

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000300

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.0172

Alfa AF: 0.00985 Hom.: 1

Bravo AF: 0.0160

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

Apr 10, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.8
Dann	Benign	0.72

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: rs16888768; hg19: chr6-24174674;