rs398124630

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_022167.4(XYLT2):c.2402C>G(p.Thr801Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,613,648 control chromosomes in the GnomAD database, including 112,784 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T801I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.33 ( 8965 hom., cov: 33)

Exomes 𝑓: 0.37 ( 103819 hom. )

Consequence

XYLT2
NM_022167.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 3.21

Publications

41 publications found

Variant links:

Genes affected

XYLT2 (HGNC:15517): (xylosyltransferase 2) The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate. The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

XYLT2 Gene-Disease associations (from GenCC):

spondylo-ocular syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

XYLT2 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=2.4977326E-4).

BP6

Variant 17-50360095-C-G is Benign according to our data. Variant chr17-50360095-C-G is described in ClinVar as Benign. ClinVar VariationId is 2533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022167.4. 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
	XYLT2	NM_022167.4	MANE Select	c.2402C>G	p.Thr801Arg	missense	Exon 11 of 11	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.2221C>G		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XYLT2	ENST00000017003.7	TSL:1 MANE Select	c.2402C>G	p.Thr801Arg	missense	Exon 11 of 11	ENSP00000017003.2	Q9H1B5-1
XYLT2	ENST00000376550.7	TSL:1	n.*286C>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000365733.3	A0A0C4DFW8
XYLT2	ENST00000376550.7	TSL:1	n.*286C>G		3_prime_UTR	Exon 10 of 10	ENSP00000365733.3	A0A0C4DFW8

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50095

AN:

152004

Hom.:

8956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.0949

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.343

GnomAD2 exomes

AF:

0.330

AC:

82635

AN:

250440

AF XY:

0.340

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.454

Gnomad EAS exome

AF:

0.0786

Gnomad FIN exome

AF:

0.403

Gnomad NFE exome

AF:

0.389

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.371

AC:

541626

AN:

1461526

Hom.:

103819

Cov.:

AF XY:

0.372

AC XY:

270374

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.231

AC:

7730

AN:

33478

American (AMR)

AF:

0.224

AC:

10013

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

11690

AN:

26136

East Asian (EAS)

AF:

0.102

AC:

4050

AN:

39698

South Asian (SAS)

AF:

0.348

AC:

29976

AN:

86244

European-Finnish (FIN)

AF:

0.403

AC:

21477

AN:

53230

Middle Eastern (MID)

AF:

0.417

AC:

2405

AN:

5766

European-Non Finnish (NFE)

AF:

0.389

AC:

432339

AN:

1111882

Other (OTH)

AF:

0.363

AC:

21946

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

22498

44997

67495

89994

112492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13240

26480

39720

52960

66200

<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:

0.329

AC:

50123

AN:

152122

Hom.:

8965

Cov.:

AF XY:

0.330

AC XY:

24526

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.230

AC:

9532

AN:

41502

American (AMR)

AF:

0.294

AC:

4493

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1553

AN:

3468

East Asian (EAS)

AF:

0.0953

AC:

493

AN:

5174

South Asian (SAS)

AF:

0.327

AC:

1578

AN:

4826

European-Finnish (FIN)

AF:

0.411

AC:

4339

AN:

10570

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26762

AN:

67964

Other (OTH)

AF:

0.342

AC:

722

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1682

3364

5046

6728

8410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.347

Hom.:

3008

Bravo

AF:

0.314

TwinsUK

AF:

0.392

AC:

1453

ALSPAC

AF:

0.396

AC:

1526

ESP6500AA

AF:

0.241

AC:

1064

ESP6500EA

AF:

0.398

AC:

3418

ExAC

AF:

0.331

AC:

40211

Asia WGS

AF:

0.196

AC:

679

AN:

3478

EpiCase

AF:

0.398

EpiControl

AF:

0.392

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Spondylo-ocular syndrome (2)

Osteogenesis imperfecta (1)

PSEUDOXANTHOMA ELASTICUM, MODIFIER OF SEVERITY OF (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.079

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.81

MetaRNN

Benign

0.00025

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

PhyloP100

3.2

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.6

REVEL

Benign

0.11

Sift

Benign

0.050

Sift4G

Uncertain

0.046

Polyphen

0.025

Vest4

0.056

MPC

0.50

ClinPred

0.011

GERP RS

1.9

Varity_R

0.063

gMVP

0.79

Mutation Taster

=92/8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over