rs2279398

Positions:

• chr5-177503768-C-T

Variant summary

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

The NM_001308236.3(DOK3):​c.*215G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,418,996 control chromosomes in the GnomAD database, including 2,137 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 0.031 (333 hom., cov: 33)
  • Exomes 𝑓: 0.015 (1804 hom.)
• Consequence: DOK3 NM_001308236.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

DOK3 (HGNC:24583): (docking protein 3) Predicted to be involved in Ras protein signal transduction and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to be located in ficolin-1-rich granule membrane and plasma membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK3	NM_001308236.3	c.*215G>A		3_prime_UTR_variant	6/6	ENST00000510898.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK3	ENST00000510898.7	c.*215G>A		3_prime_UTR_variant	6/6	3	NM_001308236.3	P1

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4693 AN: 152154 Hom.: 334 Cov.: 33

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.0694

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00240

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0154 AC: 19524 AN: 1266724 Hom.: 1804 Cov.: 30 AF XY: 0.0162 AC XY: 9936 AN XY: 612132

Gnomad4 AFR exome AF: 0.0295

Gnomad4 AMR exome AF: 0.0988

Gnomad4 ASJ exome AF: 0.00150

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.0567

Gnomad4 FIN exome AF: 0.0251

Gnomad4 NFE exome AF: 0.00129

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.0308 AC: 4696 AN: 152272 Hom.: 333 Cov.: 33 AF XY: 0.0342 AC XY: 2548 AN XY: 74430

Gnomad4 AFR AF: 0.0293

Gnomad4 AMR AF: 0.0727

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.0697

Gnomad4 FIN AF: 0.0285

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0115 Hom.: 86

Bravo AF: 0.0372

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.60

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: rs2279398; hg19: chr5-176930769;