1-205161285-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015375.3(DSTYK):c.1921T>C(p.Cys641Arg) variant causes a missense change. The variant allele was found at a frequency of 0.918 in 1,614,030 control chromosomes in the GnomAD database, including 680,196 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 66715 hom., cov: 32)

Exomes 𝑓: 0.92 ( 613481 hom. )

Consequence

DSTYK
NM_015375.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.27

Publications

54 publications found

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 Gene-Disease associations (from GenCC):

congenital anomalies of kidney and urinary tract 1
Inheritance: AD, AR Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
hereditary spastic paraplegia 23
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Orphanet
complex hereditary spastic paraplegia
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
renal agenesis, unilateral
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DSTYK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.123712E-7).

BP6

Variant 1-205161285-A-G is Benign according to our data. Variant chr1-205161285-A-G is described in ClinVar as Benign. ClinVar VariationId is 260657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DSTYK	NM_015375.3 link	c.1921T>C	p.Cys641Arg	missense_variant	Exon 7 of 13	ENST00000367162.8	NP_056190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DSTYK	ENST00000367162.8 link	c.1921T>C	p.Cys641Arg	missense_variant	Exon 7 of 13	1	NM_015375.3	ENSP00000356130.3
DSTYK	ENST00000367161.7 link	c.1921T>C	p.Cys641Arg	missense_variant	Exon 7 of 12	1		ENSP00000356129.3

Frequencies

GnomAD3 genomes

AF:

0.935

AC:

142314

AN:

152136

Hom.:

66655

Cov.:

show subpopulations

Gnomad AFR

AF:

0.984

Gnomad AMI

AF:

0.929

Gnomad AMR

AF:

0.940

Gnomad ASJ

AF:

0.917

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.951

Gnomad FIN

AF:

0.923

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.902

Gnomad OTH

AF:

0.947

GnomAD2 exomes

AF:

0.932

AC:

233925

AN:

251116

AF XY:

0.929

show subpopulations

Gnomad AFR exome

AF:

0.985

Gnomad AMR exome

AF:

0.963

Gnomad ASJ exome

AF:

0.906

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.925

Gnomad NFE exome

AF:

0.903

Gnomad OTH exome

AF:

0.921

GnomAD4 exome

AF:

0.916

AC:

1338519

AN:

1461776

Hom.:

613481

Cov.:

AF XY:

0.915

AC XY:

665735

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.989

AC:

33107

AN:

33476

American (AMR)

AF:

0.964

AC:

43091

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

23633

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39692

AN:

39700

South Asian (SAS)

AF:

0.943

AC:

81309

AN:

86254

European-Finnish (FIN)

AF:

0.922

AC:

49240

AN:

53420

Middle Eastern (MID)

AF:

0.902

AC:

5200

AN:

5766

European-Non Finnish (NFE)

AF:

0.906

AC:

1007516

AN:

1111912

Other (OTH)

AF:

0.923

AC:

55731

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

5867

11733

17600

23466

29333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21482

42964

64446

85928

107410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.936

AC:

142434

AN:

152254

Hom.:

66715

Cov.:

AF XY:

0.936

AC XY:

69673

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.984

AC:

40890

AN:

41548

American (AMR)

AF:

0.940

AC:

14370

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.917

AC:

3183

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5176

AN:

5180

South Asian (SAS)

AF:

0.951

AC:

4586

AN:

4824

European-Finnish (FIN)

AF:

0.923

AC:

9783

AN:

10602

Middle Eastern (MID)

AF:

0.932

AC:

274

AN:

294

European-Non Finnish (NFE)

AF:

0.902

AC:

61318

AN:

68014

Other (OTH)

AF:

0.948

AC:

2007

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

477

954

1430

1907

2384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.914

Hom.:

237573

Bravo

AF:

0.941

TwinsUK

AF:

0.909

AC:

3372

ALSPAC

AF:

0.914

AC:

3521

ESP6500AA

AF:

0.980

AC:

4317

ESP6500EA

AF:

0.905

AC:

7781

ExAC

AF:

0.932

AC:

113112

Asia WGS

AF:

0.982

AC:

3417

AN:

3478

EpiCase

AF:

0.899

EpiControl

AF:

0.900

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 30389748)

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital anomalies of kidney and urinary tract 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Hereditary spastic paraplegia 23

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.045

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0

.;T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.40

T;T;T

MetaRNN

Benign

9.1e-7

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

N;N;.

PhyloP100

4.3

PrimateAI

Uncertain

0.78

PROVEAN

Benign

2.2

N;N;.

REVEL

Benign

0.21

Sift

Benign

0.57

T;T;.

Sift4G

Benign

0.18

T;T;T

Vest4

0.26

ClinPred

0.0059

GERP RS

5.3

Varity_R

0.19

gMVP

0.72

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over