20-54651054-G-A

Position:

• chr20-54651054-G-A

Variant summary

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

The NM_018431.5(DOK5):​c.*575G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,164 control chromosomes in the GnomAD database, including 8,399 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 0.30 (8399 hom., cov: 33)
  • Exomes 𝑓: 0.29 (0 hom.)
• Consequence: DOK5 NM_018431.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOK5	NM_018431.5	c.*575G>A		3_prime_UTR_variant	8/8	ENST00000262593.10
DOK5	NM_177959.3	c.*575G>A		3_prime_UTR_variant	8/8
DOK5	XM_011528904.2	c.*575G>A		3_prime_UTR_variant	8/8
DOK5	XM_024451946.2	c.*575G>A		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOK5	ENST00000262593.10	c.*575G>A		3_prime_UTR_variant	8/8	1	NM_018431.5	P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45826 AN: 152018 Hom.: 8396 Cov.: 33

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.286 AC: 8 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 6 AN XY: 18

Gnomad4 AFR exome AF: 0.250

Gnomad4 NFE exome AF: 0.292

GnomAD4 genome AF: 0.301 AC: 45826 AN: 152136 Hom.: 8399 Cov.: 33 AF XY: 0.306 AC XY: 22793 AN XY: 74366

Gnomad4 AFR AF: 0.0772

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.333

Alfa AF: 0.329 Hom.: 2547

Bravo AF: 0.283

Asia WGS AF: 0.407 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.72

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: rs2841; hg19: chr20-53267593;