20-54568983-CAAAAAAAA-CAAAAAA

Variant names:

• chr20-54568983-CAA-C
• rs10542523
• NM_018431.5:c.174+13964_174+13965delAA

Variant summary

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

The NM_018431.5(DOK5):​c.174+13964_174+13965delAA 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 0.035 (77 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 (AFR) allele frequency at 95% confidence interval = 0.0721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+13964_174+13965delAA		intron_variant	Intron 2 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+13964_-151+13965delAA		intron_variant	Intron 2 of 7		NP_808874.1
DOK5	XM_024451946.2	c.138+13964_138+13965delAA		intron_variant	Intron 2 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.-151+13964_-151+13965delAA		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+13944_174+13945delAA		intron_variant	Intron 2 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.-151+13944_-151+13945delAA		intron_variant	Intron 2 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 3381 AN: 96270 Hom.: 77 Cov.: 0

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.00169

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.00754

Gnomad MID AF: 0.0153

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0293

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

GnomAD4 genome AF: 0.0352 AC: 3391 AN: 96234 Hom.: 77 Cov.: 0 AF XY: 0.0348 AC XY: 1559 AN XY: 44790

African (AFR) AF: 0.0748 AC: 2018 AN: 26962

American (AMR) AF: 0.0201 AC: 180 AN: 8944

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 56 AN: 2486

East Asian (EAS) AF: 0.0148 AC: 49 AN: 3316

South Asian (SAS) AF: 0.0128 AC: 32 AN: 2508

European-Finnish (FIN) AF: 0.00754 AC: 26 AN: 3450

Middle Eastern (MID) AF: 0.0169 AC: 3 AN: 178

European-Non Finnish (NFE) AF: 0.0212 AC: 988 AN: 46534

Other (OTH) AF: 0.0300 AC: 38 AN: 1266

Alfa AF: 0.00302 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

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;