rs873079

Variant names:

• chr20-54643947-G-A
• rs873079
• NM_018431.5:c.856+369G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018431.5(DOK5):​c.856+369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,038 control chromosomes in the GnomAD database, including 7,749 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 0.30 (7749 hom., cov: 32)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 7 publications found

Genes affected

DOK5 (HGNC:16173): (docking protein 5) The protein encoded by this gene is a member of the DOK family of membrane proteins, which are adapter proteins involved in signal transduction. The encoded protein interacts with phosphorylated receptor tyrosine kinases to mediate neurite outgrowth and activation of the MAP kinase pathway. Unlike other DOK family proteins, this protein does not interact with RASGAP. This protein is up-regulated in patients with systemic sclerosis and is associated with fibrosis induced by insulin-like growth factor binding protein 5. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018431.5. 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
	DOK5	NM_018431.5	MANE Select	c.856+369G>A		intron	N/A	NP_060901.2
	DOK5	NM_177959.3		c.532+369G>A		intron	N/A	NP_808874.1	Q9P104-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	ENST00000262593.10	TSL:1 MANE Select	c.856+369G>A		intron	N/A	ENSP00000262593.5	Q9P104-1
	DOK5	ENST00000395939.5	TSL:1	c.532+369G>A		intron	N/A	ENSP00000379270.1	Q9P104-2
	DOK5	ENST00000939307.1		c.817+369G>A		intron	N/A	ENSP00000609366.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44893 AN: 151920 Hom.: 7747 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44914 AN: 152038 Hom.: 7749 Cov.: 32 AF XY: 0.295 AC XY: 21944 AN XY: 74298

African (AFR) AF: 0.470 AC: 19504 AN: 41462

American (AMR) AF: 0.203 AC: 3102 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3468

East Asian (EAS) AF: 0.451 AC: 2319 AN: 5138

South Asian (SAS) AF: 0.222 AC: 1069 AN: 4808

European-Finnish (FIN) AF: 0.277 AC: 2922 AN: 10566

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14628 AN: 67986

Other (OTH) AF: 0.248 AC: 523 AN: 2112

Alfa AF: 0.237 Hom.: 16234

Bravo AF: 0.300

Asia WGS AF: 0.323 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.36
PhyloP100		0.17
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

Other links and lift over

dbSNP: rs873079; hg19: chr20-53260486;