rs6098009

Positions:

• chr20-54480077-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.66+4065T>C		intron_variant		ENST00000262593.10
DOK5	NM_001294161.2	c.66+4065T>C		intron_variant
DOK5	NM_177959.3	c.-259+4173T>C		intron_variant
DOK5	XM_011528904.2	c.-259+3892T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.66+4065T>C		intron_variant		1	NM_018431.5	P1
DOK5	ENST00000395939.5	c.-259+4173T>C		intron_variant		1
DOK5	ENST00000491469.1	n.387+4065T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0267

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.183

Alfa AF: 0.115 Hom.: 1504

Bravo AF: 0.219

Asia WGS AF: 0.0610 AC: 215 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs6098009; hg19: chr20-53096616;