20-54651054-G-A

Variant names:

• chr20-54651054-G-A
• rs2841
• NM_018431.5:c.*575G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018431.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	NM_018431.5	MANE Select	c.*575G>A		3_prime_UTR	Exon 8 of 8	NP_060901.2
	DOK5	NM_177959.3		c.*575G>A		3_prime_UTR	Exon 8 of 8	NP_808874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	ENST00000262593.10	TSL:1 MANE Select	c.*575G>A		3_prime_UTR	Exon 8 of 8	ENSP00000262593.5
	DOK5	ENST00000395939.5	TSL:1	c.*575G>A		downstream_gene	N/A	ENSP00000379270.1

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.292 AC: 7 AN: 24

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0772 AC: 3205 AN: 41514

American (AMR) AF: 0.330 AC: 5046 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1495 AN: 3470

East Asian (EAS) AF: 0.439 AC: 2263 AN: 5156

South Asian (SAS) AF: 0.367 AC: 1771 AN: 4828

European-Finnish (FIN) AF: 0.425 AC: 4500 AN: 10582

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26299 AN: 67984

Other (OTH) AF: 0.333 AC: 703 AN: 2112

Alfa AF: 0.297 Hom.: 4375

Bravo AF: 0.283

Asia WGS AF: 0.407 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.72
PhyloP100		0.067
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2841; hg19: chr20-53267593;