rs9319790

Variant names:

• chr18-69638045-C-T
• rs9319790
• NM_152721.6:c.289+38547C>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+38547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,134 control chromosomes in the GnomAD database, including 742 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 0.092 (742 hom., cov: 32)
• Consequence: DOK6 NM_152721.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK6	NM_152721.6	c.289+38547C>T		intron_variant	Intron 3 of 7	ENST00000382713.10	NP_689934.2
DOK6	XM_017025610.2	c.-5781C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6		XP_016881099.1
DOK6	XM_017025610.2	c.-5781C>T		5_prime_UTR_variant	Exon 1 of 6		XP_016881099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK6	ENST00000382713.10	c.289+38547C>T		intron_variant	Intron 3 of 7	1	NM_152721.6	ENSP00000372160.5

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14040 AN: 152016 Hom.: 745 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.0925 AC: 14068 AN: 152134 Hom.: 742 Cov.: 32 AF XY: 0.0931 AC XY: 6923 AN XY: 74372

African (AFR) AF: 0.111 AC: 4611 AN: 41512

American (AMR) AF: 0.161 AC: 2455 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.167 AC: 862 AN: 5158

South Asian (SAS) AF: 0.0683 AC: 329 AN: 4818

European-Finnish (FIN) AF: 0.0454 AC: 481 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4666 AN: 68002

Other (OTH) AF: 0.113 AC: 239 AN: 2106

Alfa AF: 0.0824 Hom.: 1539

Bravo AF: 0.104

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.81
PhyloP100		0.0090
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: rs9319790; hg19: chr18-67305281;