rs6023357

Variant names:

• chr20-54556389-A-C
• rs6023357
• NM_018431.5:c.174+1349A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018431.5(DOK5):​c.174+1349A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,152 control chromosomes in the GnomAD database, including 6,182 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 0.23 (6182 hom., cov: 32)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 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.174+1349A>C		intron	N/A	NP_060901.2
	DOK5	NM_177959.3		c.-151+1349A>C		intron	N/A	NP_808874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	ENST00000262593.10	TSL:1 MANE Select	c.174+1349A>C		intron	N/A	ENSP00000262593.5
	DOK5	ENST00000395939.5	TSL:1	c.-151+1349A>C		intron	N/A	ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35304 AN: 152034 Hom.: 6146 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.233 AC: 35395 AN: 152152 Hom.: 6182 Cov.: 32 AF XY: 0.228 AC XY: 16978 AN XY: 74398

African (AFR) AF: 0.500 AC: 20739 AN: 41456

American (AMR) AF: 0.197 AC: 3019 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.135 AC: 699 AN: 5184

South Asian (SAS) AF: 0.104 AC: 502 AN: 4826

European-Finnish (FIN) AF: 0.105 AC: 1118 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8454 AN: 67996

Other (OTH) AF: 0.204 AC: 431 AN: 2114

Alfa AF: 0.190 Hom.: 631

Bravo AF: 0.253

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.61
PhyloP100		0.057
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: rs6023357; hg19: chr20-53172928;