rs6068915

Variant names:

• chr20-54610242-C-A
• rs6068915
• NM_018431.5:c.600-146C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-54610242-C-A
• chr20-54610242-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018431.5(DOK5):​c.600-146C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 692,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DOK5 NM_018431.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK5	NM_018431.5	c.600-146C>A		intron_variant	Intron 5 of 7	ENST00000262593.10	NP_060901.2
DOK5	NM_177959.3	c.276-146C>A		intron_variant	Intron 5 of 7		NP_808874.1
DOK5	XM_024451946.2	c.564-146C>A		intron_variant	Intron 5 of 7		XP_024307714.1
DOK5	XM_011528904.2	c.276-146C>A		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.600-146C>A		intron_variant	Intron 5 of 7	1	NM_018431.5	ENSP00000262593.5
DOK5	ENST00000395939.5	c.276-146C>A		intron_variant	Intron 5 of 7	1		ENSP00000379270.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000144 AC: 1 AN: 692976 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 339502

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

African (AFR) AF: 0.00 AC: 0 AN: 16106

American (AMR) AF: 0.00 AC: 0 AN: 9356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12444

East Asian (EAS) AF: 0.00 AC: 0 AN: 26278

South Asian (SAS) AF: 0.00 AC: 0 AN: 16096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 554282

Other (OTH) AF: 0.0000319 AC: 1 AN: 31310

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.32
PhyloP100		0.026

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: rs6068915; hg19: chr20-53226781;