20-54532944-C-T

Variant names:

• chr20-54532944-C-T
• rs2426531
• NM_018431.5:c.67-21989C>T

Variant summary

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

The NM_018431.5(DOK5):​c.67-21989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,230 control chromosomes in the GnomAD database, including 4,723 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 0.17 (4723 hom., cov: 33)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.595
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	NM_018431.5	MANE Select	c.67-21989C>T		intron	N/A	NP_060901.2
	DOK5	NM_177959.3		c.-258-21989C>T		intron	N/A	NP_808874.1	Q9P104-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK5	ENST00000262593.10	TSL:1 MANE Select	c.67-21989C>T		intron	N/A	ENSP00000262593.5	Q9P104-1
	DOK5	ENST00000395939.5	TSL:1	c.-258-21989C>T		intron	N/A	ENSP00000379270.1	Q9P104-2
	DOK5	ENST00000939307.1		c.67-21989C>T		intron	N/A	ENSP00000609366.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25581 AN: 152112 Hom.: 4694 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.0788

Gnomad FIN AF: 0.0362

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0374

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.169 AC: 25669 AN: 152230 Hom.: 4723 Cov.: 33 AF XY: 0.164 AC XY: 12229 AN XY: 74446

African (AFR) AF: 0.466 AC: 19319 AN: 41484

American (AMR) AF: 0.137 AC: 2094 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 88 AN: 3472

East Asian (EAS) AF: 0.0988 AC: 512 AN: 5180

South Asian (SAS) AF: 0.0780 AC: 377 AN: 4832

European-Finnish (FIN) AF: 0.0362 AC: 384 AN: 10620

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0374 AC: 2547 AN: 68028

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Alfa AF: 0.0840 Hom.: 2059

Bravo AF: 0.191

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2426531; hg19: chr20-53149483;