20-54592054-A-C

Variant names:

• chr20-54592054-A-C
• rs6098099
• NM_018431.5:c.599+249A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018431.5(DOK5):​c.599+249A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,298 control chromosomes in the GnomAD database, including 350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.064 (350 hom., cov: 32)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.599+249A>C		intron_variant	Intron 5 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.275+249A>C		intron_variant	Intron 5 of 7		NP_808874.1
DOK5	XM_024451946.2	c.563+249A>C		intron_variant	Intron 5 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.275+249A>C		intron_variant	Intron 5 of 7		XP_011527206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK5	ENST00000262593.10	c.599+249A>C		intron_variant	Intron 5 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.275+249A>C		intron_variant	Intron 5 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9790 AN: 152180 Hom.: 350 Cov.: 32

Gnomad AFR AF: 0.0705

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0316

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0643 AC: 9789 AN: 152298 Hom.: 350 Cov.: 32 AF XY: 0.0614 AC XY: 4576 AN XY: 74474

African (AFR) AF: 0.0703 AC: 2922 AN: 41548

American (AMR) AF: 0.0691 AC: 1058 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0866 AC: 300 AN: 3464

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4830

European-Finnish (FIN) AF: 0.0316 AC: 336 AN: 10620

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0716 AC: 4871 AN: 68032

Other (OTH) AF: 0.0787 AC: 166 AN: 2110

Alfa AF: 0.0735 Hom.: 760

Bravo AF: 0.0681

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0090
DANN	Benign	0.65
PhyloP100		-1.2
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: rs6098099; hg19: chr20-53208593;