20-54568983-CAAAAAAAA-CAAAAA

Variant names:

• chr20-54568983-CAAA-C
• rs10542523
• NM_018431.5:c.174+13963_174+13965delAAA

Variant summary

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

The NM_018431.5(DOK5):​c.174+13963_174+13965delAAA 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 0.011 (15 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 = 0.0113 (1087/96172) while in subpopulation AFR AF = 0.0372 (1001/26932). AF 95% confidence interval is 0.0353. There are 15 homozygotes in GnomAd4. There are 494 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+13963_174+13965delAAA		intron_variant	Intron 2 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+13963_-151+13965delAAA		intron_variant	Intron 2 of 7		NP_808874.1
DOK5	XM_024451946.2	c.138+13963_138+13965delAAA		intron_variant	Intron 2 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.-151+13963_-151+13965delAAA		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+13946delAAA		intron_variant	Intron 2 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.-151+13944_-151+13946delAAA		intron_variant	Intron 2 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1086 AN: 96208 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00470

Gnomad ASJ AF: 0.000403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00145

Gnomad MID AF: 0.00510

Gnomad NFE AF: 0.000516

Gnomad OTH AF: 0.0103

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

GnomAD4 genome AF: 0.0113 AC: 1087 AN: 96172 Hom.: 15 Cov.: 0 AF XY: 0.0110 AC XY: 494 AN XY: 44766

African (AFR) AF: 0.0372 AC: 1001 AN: 26932

American (AMR) AF: 0.00470 AC: 42 AN: 8938

Ashkenazi Jewish (ASJ) AF: 0.000403 AC: 1 AN: 2484

East Asian (EAS) AF: 0.00 AC: 0 AN: 3318

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

European-Finnish (FIN) AF: 0.00145 AC: 5 AN: 3446

Middle Eastern (MID) AF: 0.00562 AC: 1 AN: 178

European-Non Finnish (NFE) AF: 0.000516 AC: 24 AN: 46514

Other (OTH) AF: 0.0103 AC: 13 AN: 1266

Alfa AF: 0.00 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;