chr20-54568983-CAAAAA-C

Variant names:

• chr20-54568983-CAAAAA-C
• rs10542523
• NM_018431.5:c.174+13961_174+13965delAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018431.5(DOK5):​c.174+13961_174+13965delAAAAA 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 0.000010 (0 hom., cov: 0)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.174+13961_174+13965delAAAAA		intron_variant	Intron 2 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.-151+13961_-151+13965delAAAAA		intron_variant	Intron 2 of 7		NP_808874.1
DOK5	XM_024451946.2	c.138+13961_138+13965delAAAAA		intron_variant	Intron 2 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.-151+13961_-151+13965delAAAAA		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+13948delAAAAA		intron_variant	Intron 2 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.-151+13944_-151+13948delAAAAA		intron_variant	Intron 2 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.0000104 AC: 1 AN: 96232 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000215

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000104 AC: 1 AN: 96232 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 44784

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26900

American (AMR) AF: 0.00 AC: 0 AN: 8944

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3336

South Asian (SAS) AF: 0.00 AC: 0 AN: 2530

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 196

European-Non Finnish (NFE) AF: 0.0000215 AC: 1 AN: 46540

Other (OTH) AF: 0.00 AC: 0 AN: 1262

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43

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;