chr6-24172734-C-A

Position:

• chr6-24172734-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016356.5(DCDC2):​c.*1996G>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 0.0824 in 152,108 control chromosomes in the GnomAD database, including 698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (698 hom., cov: 31)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: DCDC2 NM_016356.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_016356.5	c.*1996G>T		3_prime_UTR_variant	10/10	ENST00000378454.8	NP_057440.2
DCDC2	NM_001195610.2	c.*1996G>T		3_prime_UTR_variant	11/11		NP_001182539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCDC2	ENST00000378454.8	c.*1996G>T		3_prime_UTR_variant	10/10	1	NM_016356.5	ENSP00000367715	P1
DCDC2	ENST00000378450.6	c.*1996G>T		3_prime_UTR_variant	3/3	1		ENSP00000367711

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12524 AN: 151974 Hom.: 700 Cov.: 31

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.0912

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0824 AC: 12527 AN: 152092 Hom.: 698 Cov.: 31 AF XY: 0.0841 AC XY: 6255 AN XY: 74348

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0505

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.0814 Hom.: 60

Bravo AF: 0.0800

Asia WGS AF: 0.180 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.38

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: rs1832709; hg19: chr6-24172962;