20-54568983-CAAAAAAAA-CAAAAAAAAA

Variant names:

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

Variant summary

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

The NM_018431.5(DOK5):​c.174+13965dupA 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 0.040 (193 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 = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+13965dupA		intron_variant	Intron 2 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+13965dupA		intron_variant	Intron 2 of 7		NP_808874.1
DOK5	XM_024451946.2	c.138+13965dupA		intron_variant	Intron 2 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.-151+13965dupA		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+13943_174+13944insA		intron_variant	Intron 2 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.-151+13943_-151+13944insA		intron_variant	Intron 2 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 3831 AN: 96148 Hom.: 193 Cov.: 0

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.00323

Gnomad EAS AF: 0.00420

Gnomad SAS AF: 0.00356

Gnomad FIN AF: 0.000870

Gnomad MID AF: 0.0153

Gnomad NFE AF: 0.00658

Gnomad OTH AF: 0.0310

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

GnomAD4 genome AF: 0.0399 AC: 3838 AN: 96112 Hom.: 193 Cov.: 0 AF XY: 0.0387 AC XY: 1731 AN XY: 44744

African (AFR) AF: 0.122 AC: 3283 AN: 26882

American (AMR) AF: 0.0194 AC: 173 AN: 8936

Ashkenazi Jewish (ASJ) AF: 0.00323 AC: 8 AN: 2480

East Asian (EAS) AF: 0.00422 AC: 14 AN: 3318

South Asian (SAS) AF: 0.00359 AC: 9 AN: 2506

European-Finnish (FIN) AF: 0.000870 AC: 3 AN: 3448

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

European-Non Finnish (NFE) AF: 0.00658 AC: 306 AN: 46510

Other (OTH) AF: 0.0309 AC: 39 AN: 1264

Alfa AF: 0.00841 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;