20-54643425-G-C

Position:

• chr20-54643425-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018431.5(DOK5):​c.736-33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,609,122 control chromosomes in the GnomAD database, including 71,834 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 0.36 (10762 hom., cov: 33)
  • Exomes 𝑓: 0.28 (61072 hom.)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.736-33G>C		intron_variant		ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.412-33G>C		intron_variant			NP_808874.1
DOK5	XM_024451946.2	c.700-33G>C		intron_variant			XP_024307714.1
DOK5	XM_011528904.2	c.412-33G>C		intron_variant			XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.736-33G>C		intron_variant		1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.412-33G>C		intron_variant		1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54046 AN: 151990 Hom.: 10758 Cov.: 33

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.327

GnomAD3 exomes AF: 0.298 AC: 73453 AN: 246446 Hom.: 11919 AF XY: 0.292 AC XY: 38883 AN XY: 133374

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.435

Gnomad SAS exome AF: 0.237

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.284 AC: 413408 AN: 1457014 Hom.: 61072 Cov.: 34 AF XY: 0.281 AC XY: 203289 AN XY: 724560

Gnomad4 AFR exome AF: 0.559

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.287

GnomAD4 genome AF: 0.356 AC: 54077 AN: 152108 Hom.: 10762 Cov.: 33 AF XY: 0.354 AC XY: 26345 AN XY: 74348

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.324

Alfa AF: 0.301 Hom.: 1402

Bravo AF: 0.364

Asia WGS AF: 0.336 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.71
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6064099; hg19: chr20-53259964; COSMIC: COSV52821487;