Variant rs148815814 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_015375.3(DSTYK):c.1775G>A(p.Arg592Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,614,004 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R592W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

DSTYK
NM_015375.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 7.91

Variant links:

Genes affected

DSTYK (HGNC:29043): (dual serine/threonine and tyrosine protein kinase) This gene encodes a dual serine/threonine and tyrosine protein kinase which is expressed in multiple tissues. It is thought to function as a regulator of cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

DSTYK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032061845).

BP6

Variant 1-205162079-C-T is Benign according to our data. Variant chr1-205162079-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 224356.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 188 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSTYK	NM_015375.3 linkuse as main transcript	c.1775G>A	p.Arg592Gln	missense_variant	6/13	ENST00000367162.8	NP_056190.1	Q6XUX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSTYK	ENST00000367162.8 linkuse as main transcript	c.1775G>A	p.Arg592Gln	missense_variant	6/13	1	NM_015375.3	ENSP00000356130.3		Q6XUX3-1
DSTYK	ENST00000367161.7 linkuse as main transcript	c.1775G>A	p.Arg592Gln	missense_variant	6/12	1		ENSP00000356129.3		Q6XUX3-2

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

188

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00408

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000334

AC:

AN:

251238

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000708

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000152

AC:

222

AN:

1461832

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00376

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00166

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.00124

AC:

188

AN:

152172

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00407

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000301

Hom.:

Bravo

AF:

0.00139

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000362

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Congenital anomalies of kidney and urinary tract 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 23, 2023

- -

DSTYK-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.090

.;T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.9

D;D;.

REVEL

Uncertain

0.61

Sift

Uncertain

0.0060

D;D;.

Sift4G

Uncertain

0.019

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.75

MVP

0.91

MPC

1.2

ClinPred

0.094

GERP RS

5.9

Varity_R

0.38

gMVP

0.63

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