chr20-54610242-C-T

Position:

• chr20-54610242-C-T

Variant summary

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

The ENST00000262593.10(DOK5):​c.600-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 843,342 control chromosomes in the GnomAD database, including 66,012 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 (21561 hom., cov: 34)
  • Exomes 𝑓: 0.34 (44451 hom.)
• Consequence: DOK5 ENST00000262593.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOK5	NM_018431.5	c.600-146C>T		intron_variant		ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.276-146C>T		intron_variant			NP_808874.1
DOK5	XM_011528904.2	c.276-146C>T		intron_variant			XP_011527206.1
DOK5	XM_024451946.2	c.564-146C>T		intron_variant			XP_024307714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.600-146C>T		intron_variant		1	NM_018431.5	ENSP00000262593	P1
DOK5	ENST00000395939.5	c.276-146C>T		intron_variant		1		ENSP00000379270

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70899 AN: 152120 Hom.: 21499 Cov.: 34

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.338 AC: 233371 AN: 691104 Hom.: 44451 AF XY: 0.335 AC XY: 113582 AN XY: 338580

Gnomad4 AFR exome AF: 0.877

Gnomad4 AMR exome AF: 0.463

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.467 AC: 71040 AN: 152238 Hom.: 21561 Cov.: 34 AF XY: 0.453 AC XY: 33717 AN XY: 74440

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.00521

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.445

Alfa AF: 0.422 Hom.: 2052

Bravo AF: 0.504

Asia WGS AF: 0.136 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.41

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: rs6068915; hg19: chr20-53226781;