chr18-69822170-G-A

Variant names:

• chr18-69822170-G-A
• rs10513978
• NM_152721.6:c.857-19074G>A

Variant summary

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

The NM_152721.6(DOK6):​c.857-19074G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,996 control chromosomes in the GnomAD database, including 5,254 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 0.26 (5254 hom., cov: 32)
• Consequence: DOK6 NM_152721.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOK6	NM_152721.6	c.857-19074G>A		intron_variant	Intron 7 of 7	ENST00000382713.10	NP_689934.2
DOK6	XM_017025610.2	c.533-19074G>A		intron_variant	Intron 5 of 5		XP_016881099.1
DOK6	XM_017025611.2	c.533-19074G>A		intron_variant	Intron 5 of 5		XP_016881100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOK6	ENST00000382713.10	c.857-19074G>A		intron_variant	Intron 7 of 7	1	NM_152721.6	ENSP00000372160.5

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39904 AN: 151878 Hom.: 5251 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.263 AC: 39932 AN: 151996 Hom.: 5254 Cov.: 32 AF XY: 0.265 AC XY: 19688 AN XY: 74258

African (AFR) AF: 0.256 AC: 10615 AN: 41440

American (AMR) AF: 0.219 AC: 3347 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3472

East Asian (EAS) AF: 0.248 AC: 1280 AN: 5170

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4820

European-Finnish (FIN) AF: 0.335 AC: 3536 AN: 10558

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18487 AN: 67964

Other (OTH) AF: 0.251 AC: 531 AN: 2114

Alfa AF: 0.262 Hom.: 863

Bravo AF: 0.251

Asia WGS AF: 0.245 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.68
PhyloP100		1.0
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: rs10513978; hg19: chr18-67489406; COSMIC: COSV66937420;