chr20-54568983-CA-C

Variant names:

• chr20-54568983-CA-C
• rs10542523
• NM_018431.5:c.174+13965delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018431.5(DOK5):​c.174+13965delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.73 (25862 hom., cov: 0)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+13965delA		intron_variant	Intron 2 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+13965delA		intron_variant	Intron 2 of 7		NP_808874.1
DOK5	XM_024451946.2	c.138+13965delA		intron_variant	Intron 2 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.-151+13965delA		intron_variant	Intron 2 of 7		XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.174+13944delA		intron_variant	Intron 2 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.-151+13944delA		intron_variant	Intron 2 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 70319 AN: 96222 Hom.: 25887 Cov.: 0

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.776

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.731 AC: 70266 AN: 96186 Hom.: 25862 Cov.: 0 AF XY: 0.733 AC XY: 32826 AN XY: 44758

African (AFR) AF: 0.490 AC: 13159 AN: 26878

American (AMR) AF: 0.811 AC: 7246 AN: 8934

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2016 AN: 2490

East Asian (EAS) AF: 0.769 AC: 2560 AN: 3330

South Asian (SAS) AF: 0.879 AC: 2203 AN: 2506

European-Finnish (FIN) AF: 0.906 AC: 3128 AN: 3454

Middle Eastern (MID) AF: 0.775 AC: 138 AN: 178

European-Non Finnish (NFE) AF: 0.823 AC: 38334 AN: 46560

Other (OTH) AF: 0.723 AC: 915 AN: 1266

Alfa AF: 0.691 Hom.: 1186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
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: rs10542523; hg19: chr20-53185522;