Variant 18-69677794-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152721.6(DOK6):c.350A>G(p.Asn117Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,613,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

DOK6
NM_152721.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

Variant links:

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]

DOK6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DOK6	NM_152721.6 linkuse as main transcript	c.350A>G	p.Asn117Ser	missense_variant	4/8	ENST00000382713.10
DOK6	XM_017025610.2 linkuse as main transcript	c.26A>G	p.Asn9Ser	missense_variant	2/6
DOK6	XM_017025611.2 linkuse as main transcript	c.26A>G	p.Asn9Ser	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DOK6	ENST00000382713.10 linkuse as main transcript	c.350A>G	p.Asn117Ser	missense_variant	4/8	1	NM_152721.6	P1
DOK6	ENST00000582992.1 linkuse as main transcript	c.62A>G	p.Asn21Ser	missense_variant	1/3	3
DOK6	ENST00000582172.5 linkuse as main transcript	n.321A>G		non_coding_transcript_exon_variant	3/4	3
DOK6	ENST00000584435.1 linkuse as main transcript	n.164A>G		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251428

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000281

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000246

AC:

359

AN:

1461602

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000315

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000125

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000383

Hom.:

Bravo

AF:

0.000117

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2023

The c.350A>G (p.N117S) alteration is located in exon 4 (coding exon 4) of the DOK6 gene. This alteration results from a A to G substitution at nucleotide position 350, causing the asparagine (N) at amino acid position 117 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.075

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.31

Sift

Benign

0.21

Sift4G

Benign

0.13

Polyphen

0.40

Vest4

0.68

MVP

0.82

MPC

0.37

ClinPred

0.11

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.42

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over