chr1-205211450-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015375.3(DSTYK):c.86G>A(p.Arg29Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000658 in 1,599,294 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00065 ( 2 hom. )

Consequence

DSTYK
NM_015375.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:2B:4

Conservation

PhyloP100: 4.21

Publications

4 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary spastic paraplegia 23
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012831062).

BP6

Variant 1-205211450-C-T is Benign according to our data. Variant chr1-205211450-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 60687.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000722 (110/152342) while in subpopulation AMR AF = 0.00209 (32/15310). AF 95% confidence interval is 0.00152. There are 0 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015375.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DSTYK	NM_015375.3	MANE Select	c.86G>A	p.Arg29Gln	missense	Exon 1 of 13	NP_056190.1	Q6XUX3-1
	DSTYK	NM_199462.3		c.86G>A	p.Arg29Gln	missense	Exon 1 of 12	NP_955749.1	Q6XUX3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DSTYK	ENST00000367162.8	TSL:1 MANE Select	c.86G>A	p.Arg29Gln	missense	Exon 1 of 13	ENSP00000356130.3	Q6XUX3-1
DSTYK	ENST00000367161.7	TSL:1	c.86G>A	p.Arg29Gln	missense	Exon 1 of 12	ENSP00000356129.3	Q6XUX3-2
DSTYK	ENST00000893236.1		c.86G>A	p.Arg29Gln	missense	Exon 1 of 13	ENSP00000563295.1

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

110

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00101

AC:

223

AN:

220688

AF XY:

0.00123

show subpopulations

Gnomad AFR exome

AF:

0.0000745

Gnomad AMR exome

AF:

0.000545

Gnomad ASJ exome

AF:

0.00786

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000738

Gnomad OTH exome

AF:

0.000547

GnomAD4 exome

AF:

0.000651

AC:

942

AN:

1446952

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

527

AN XY:

719528

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

33058

American (AMR)

AF:

0.000797

AC:

AN:

43906

Ashkenazi Jewish (ASJ)

AF:

0.00894

AC:

231

AN:

25852

East Asian (EAS)

AF:

0.00

AC:

AN:

39256

South Asian (SAS)

AF:

0.00169

AC:

144

AN:

85056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46182

Middle Eastern (MID)

AF:

0.00175

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.000417

AC:

462

AN:

1108036

Other (OTH)

AF:

0.000935

AC:

AN:

59888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

120

180

240

300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000722

AC:

110

AN:

152342

Hom.:

Cov.:

AF XY:

0.000805

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41580

American (AMR)

AF:

0.00209

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00112

Hom.:

Bravo

AF:

0.000907

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000669

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Congenital anomalies of kidney and urinary tract 1 (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.013

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

1.4

PhyloP100

4.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.75

REVEL

Uncertain

0.38

Sift

Benign

0.45

Sift4G

Benign

0.36

Polyphen

1.0

Vest4

0.56

MutPred

0.41

Loss of loop (P = 0.0073)

MVP

0.83

MPC

0.62

ClinPred

0.21

GERP RS

5.2

PromoterAI

0.033

Neutral

(source)

Varity_R

0.45

gMVP

0.51

Mutation Taster

=10/90

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over