20-54651096-C-G

Position:

• chr20-54651096-C-G

Variant summary

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

The NM_018431.5(DOK5):​c.*617C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,932 control chromosomes in the GnomAD database, including 17,046 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 0.45 (17046 hom., cov: 33)
  • Exomes 𝑓: 0.43 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: DOK5 NM_018431.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.*617C>G		3_prime_UTR_variant	8/8	ENST00000262593.10
DOK5	NM_177959.3	c.*617C>G		3_prime_UTR_variant	8/8
DOK5	XM_011528904.2	c.*617C>G		3_prime_UTR_variant	8/8
DOK5	XM_024451946.2	c.*617C>G		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.*617C>G		3_prime_UTR_variant	8/8	1	NM_018431.5	P1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68248 AN: 151812 Hom.: 17034 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.522

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.433 AC: 13 AN: 30 Hom.: 3 Cov.: 0 AF XY: 0.409 AC XY: 9 AN XY: 22

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.409

GnomAD4 genome AF: 0.449 AC: 68291 AN: 151932 Hom.: 17046 Cov.: 33 AF XY: 0.451 AC XY: 33517 AN XY: 74242

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.526

Alfa AF: 0.483 Hom.: 2328

Bravo AF: 0.438

Asia WGS AF: 0.501 AC: 1745 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.025
DANN	Benign	0.45

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: rs2843; hg19: chr20-53267635;