20-54616992-T-G

Variant names:

• chr20-54616992-T-G
• rs6068916
• NM_018431.5:c.735+6469T>G

Variant summary

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

The NM_018431.5(DOK5):​c.735+6469T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,732 control chromosomes in the GnomAD database, including 21,471 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 0.47 (21471 hom., cov: 30)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.27
• Publications: 3 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 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.735+6469T>G		intron	N/A	NP_060901.2
	DOK5	NM_177959.3		c.411+6469T>G		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.735+6469T>G		intron	N/A	ENSP00000262593.5	Q9P104-1
	DOK5	ENST00000395939.5	TSL:1	c.411+6469T>G		intron	N/A	ENSP00000379270.1	Q9P104-2
	DOK5	ENST00000939307.1		c.696+6469T>G		intron	N/A	ENSP00000609366.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70539 AN: 151616 Hom.: 21405 Cov.: 30

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.00503

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.466 AC: 70677 AN: 151732 Hom.: 21471 Cov.: 30 AF XY: 0.452 AC XY: 33517 AN XY: 74138

African (AFR) AF: 0.853 AC: 35284 AN: 41386

American (AMR) AF: 0.448 AC: 6822 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1135 AN: 3462

East Asian (EAS) AF: 0.00484 AC: 25 AN: 5160

South Asian (SAS) AF: 0.126 AC: 608 AN: 4812

European-Finnish (FIN) AF: 0.235 AC: 2473 AN: 10512

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23072 AN: 67862

Other (OTH) AF: 0.442 AC: 928 AN: 2098

Alfa AF: 0.202 Hom.: 359

Bravo AF: 0.504

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.29
PhyloP100		-5.3
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: rs6068916; hg19: chr20-53233531;