20-54568983-CAAAAAAAA-CAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018431.5(DOK5):​c.174+13964_174+13965dupAA 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 0.0054 (6 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.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0054 (519/96176) while in subpopulation AFR AF = 0.0181 (487/26916). AF 95% confidence interval is 0.0168. There are 6 homozygotes in GnomAd4. There are 256 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+13964_174+13965dupAA		intron_variant	Intron 2 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+13964_-151+13965dupAA		intron_variant	Intron 2 of 7		NP_808874.1
DOK5	XM_024451946.2	c.138+13964_138+13965dupAA		intron_variant	Intron 2 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.-151+13964_-151+13965dupAA		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+13944insAA		intron_variant	Intron 2 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.-151+13943_-151+13944insAA		intron_variant	Intron 2 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 519 AN: 96212 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000600

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00634

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

GnomAD4 genome AF: 0.00540 AC: 519 AN: 96176 Hom.: 6 Cov.: 0 AF XY: 0.00572 AC XY: 256 AN XY: 44772

African (AFR) AF: 0.0181 AC: 487 AN: 26916

American (AMR) AF: 0.00123 AC: 11 AN: 8940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2486

East Asian (EAS) AF: 0.000603 AC: 2 AN: 3316

South Asian (SAS) AF: 0.00 AC: 0 AN: 2506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.000236 AC: 11 AN: 46530

Other (OTH) AF: 0.00632 AC: 8 AN: 1266

Alfa AF: 0.000647 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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10542523; hg19: chr20-53185522;