rs6098009

Variant names:

• chr20-54480077-T-C
• rs6098009
• NM_018431.5:c.66+4065T>C

Variant summary

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

The NM_018431.5(DOK5):​c.66+4065T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,012 control chromosomes in the GnomAD database, including 5,205 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 0.20 (5205 hom., cov: 32)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	NM_018431.5	MANE Select	c.66+4065T>C		intron	N/A	NP_060901.2
	DOK5	NM_177959.3		c.-259+4173T>C		intron	N/A	NP_808874.1
	DOK5	NM_001294161.2		c.66+4065T>C		intron	N/A	NP_001281090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	ENST00000262593.10	TSL:1 MANE Select	c.66+4065T>C		intron	N/A	ENSP00000262593.5
	DOK5	ENST00000395939.5	TSL:1	c.-259+4173T>C		intron	N/A	ENSP00000379270.1
	DOK5	ENST00000491469.1	TSL:2	n.387+4065T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30510 AN: 151894 Hom.: 5184 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0268

Gnomad SAS AF: 0.0440

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.201 AC: 30583 AN: 152012 Hom.: 5205 Cov.: 32 AF XY: 0.193 AC XY: 14382 AN XY: 74326

African (AFR) AF: 0.469 AC: 19409 AN: 41384

American (AMR) AF: 0.139 AC: 2116 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3468

East Asian (EAS) AF: 0.0267 AC: 138 AN: 5178

South Asian (SAS) AF: 0.0440 AC: 212 AN: 4814

European-Finnish (FIN) AF: 0.0720 AC: 764 AN: 10604

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7231 AN: 67982

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.134 Hom.: 6329

Bravo AF: 0.219

Asia WGS AF: 0.0610 AC: 215 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.43
DANN	Benign	0.40
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

Other links and lift over

dbSNP: rs6098009; hg19: chr20-53096616;