rs753694334

Variant names:

• chr20-54591744-C-G
• rs753694334
• NM_018431.5:c.538C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-54591744-C-G
• chr20-54591744-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018431.5(DOK5):​c.538C>G​(p.Pro180Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOK5 NM_018431.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.538C>G	p.Pro180Ala	missense_variant	Exon 5 of 8	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.214C>G	p.Pro72Ala	missense_variant	Exon 5 of 8		NP_808874.1
DOK5	XM_024451946.2	c.502C>G	p.Pro168Ala	missense_variant	Exon 5 of 8		XP_024307714.1
DOK5	XM_011528904.2	c.214C>G	p.Pro72Ala	missense_variant	Exon 5 of 8		XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.538C>G	p.Pro180Ala	missense_variant	Exon 5 of 8	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.214C>G	p.Pro72Ala	missense_variant	Exon 5 of 8	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	0.73	D
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-6.9	D;D
REVEL	Pathogenic	0.88
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;D
Vest4		0.90
MutPred		0.89		Loss of loop (P = 0.0374);.;
MVP		0.97
MPC		1.1
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs753694334; hg19: chr20-53208283;