rs2279398

Variant names:

• chr5-177503768-C-T
• rs2279398
• NM_001308236.3:c.*215G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

PDLIM7-AS1 (HGNC:41004): (PDLIM7 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308236.3. 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
	DOK3	NM_001308236.3	MANE Select	c.*215G>A		3_prime_UTR	Exon 6 of 6	NP_001295165.1	D6RAM3
	DOK3	NM_001308235.3		c.*215G>A		3_prime_UTR	Exon 6 of 6	NP_001295164.1	D6RAM3
	DOK3	NM_001375794.1		c.*215G>A		3_prime_UTR	Exon 6 of 6	NP_001362723.1	D6RAM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK3	ENST00000510898.7	TSL:3 MANE Select	c.*215G>A		3_prime_UTR	Exon 6 of 6	ENSP00000424726.2	D6RAM3
	DOK3	ENST00000312943.10	TSL:1	c.646-376G>A		intron	N/A	ENSP00000325174.6	Q7L591-3
	DOK3	ENST00000500323.2	TSL:1	n.915-376G>A		intron	N/A

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

African (AFR) AF: 0.0295 AC: 824 AN: 27908

American (AMR) AF: 0.0988 AC: 1699 AN: 17194

Ashkenazi Jewish (ASJ) AF: 0.00150 AC: 28 AN: 18676

East Asian (EAS) AF: 0.297 AC: 9984 AN: 33624

South Asian (SAS) AF: 0.0567 AC: 3383 AN: 59654

European-Finnish (FIN) AF: 0.0251 AC: 740 AN: 29454

Middle Eastern (MID) AF: 0.00932 AC: 33 AN: 3540

European-Non Finnish (NFE) AF: 0.00129 AC: 1321 AN: 1024144

Other (OTH) AF: 0.0288 AC: 1512 AN: 52530

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

African (AFR) AF: 0.0293 AC: 1218 AN: 41564

American (AMR) AF: 0.0727 AC: 1112 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1479 AN: 5162

South Asian (SAS) AF: 0.0697 AC: 336 AN: 4822

European-Finnish (FIN) AF: 0.0285 AC: 302 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00240 AC: 163 AN: 68016

Other (OTH) AF: 0.0369 AC: 78 AN: 2116

Alfa AF: 0.0141 Hom.: 122

Bravo AF: 0.0372

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.60
PhyloP100		-1.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2279398;

hg19: chr5-176930769;