18-69609486-G-T

Variant names:

• chr18-69609486-G-T
• rs4555246
• NM_152721.6:c.289+9988G>T

Variant summary

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

The NM_152721.6(DOK6):​c.289+9988G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 148,206 control chromosomes in the GnomAD database, including 55,352 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 0.86 (55352 hom., cov: 29)
• Consequence: DOK6 NM_152721.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 1 publications found

Genes affected

DOK6 (HGNC:28301): (docking protein 6) DOK6 is a member of the DOK (see DOK1; MIM 602919) family of intracellular adaptors that play a role in the RET (MIM 164761) signaling cascade (Crowder et al., 2004 [PubMed 15286081]).[supplied by OMIM, Mar 2008]

ENSG00000265643 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK6	NM_152721.6	c.289+9988G>T		intron_variant	Intron 3 of 7	ENST00000382713.10	NP_689934.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK6	ENST00000382713.10	c.289+9988G>T		intron_variant	Intron 3 of 7	1	NM_152721.6	ENSP00000372160.5
ENSG00000265643	ENST00000583991.1	n.151+9058C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.861 AC: 127580 AN: 148104 Hom.: 55343 Cov.: 29

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.861 AC: 127636 AN: 148206 Hom.: 55352 Cov.: 29 AF XY: 0.863 AC XY: 62536 AN XY: 72494

African (AFR) AF: 0.674 AC: 25892 AN: 38404

American (AMR) AF: 0.874 AC: 13254 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3140 AN: 3464

East Asian (EAS) AF: 0.953 AC: 4920 AN: 5164

South Asian (SAS) AF: 0.860 AC: 4126 AN: 4796

European-Finnish (FIN) AF: 0.942 AC: 9525 AN: 10108

Middle Eastern (MID) AF: 0.877 AC: 256 AN: 292

European-Non Finnish (NFE) AF: 0.940 AC: 63781 AN: 67826

Other (OTH) AF: 0.883 AC: 1834 AN: 2078

Alfa AF: 0.921 Hom.: 2011

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.56
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: rs4555246; hg19: chr18-67276722;