17-50353660-G-A

Position:

chr17-50353660-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022167.4(XYLT2):c.166G>A(p.Asp56Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0135 in 1,566,816 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 32)

Exomes 𝑓: 0.014 ( 169 hom. )

Consequence

XYLT2
NM_022167.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.71

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 links:

XYLT2 (HGNC:):

XYLT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004224777).

BP6

Variant 17-50353660-G-A is Benign according to our data. Variant chr17-50353660-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1299780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50353660-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0101 (1541/152272) while in subpopulation NFE AF= 0.0154 (1045/68008). AF 95% confidence interval is 0.0146. There are 14 homozygotes in gnomad4. There are 704 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLT2	NM_022167.4 linkuse as main transcript	c.166G>A	p.Asp56Asn	missense_variant	2/11	ENST00000017003.7	NP_071450.2	Q9H1B5-1B4DT06
XYLT2	XM_005257572.5 linkuse as main transcript	c.70G>A	p.Asp24Asn	missense_variant	2/11		XP_005257629.1
XYLT2	XM_047436522.1 linkuse as main transcript	c.-426G>A		5_prime_UTR_variant	2/11		XP_047292478.1
XYLT2	NR_110010.2 linkuse as main transcript	n.181G>A		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
XYLT2	ENST00000017003.7 linkuse as main transcript	c.166G>A	p.Asp56Asn	missense_variant	2/11	1	NM_022167.4	ENSP00000017003.2	Q9H1B5-1
XYLT2	ENST00000376550.7 linkuse as main transcript	n.166G>A		non_coding_transcript_exon_variant	2/10	1		ENSP00000365733.3	A0A0C4DFW8
XYLT2	ENST00000507602.5 linkuse as main transcript	c.166G>A	p.Asp56Asn	missense_variant	2/10	2		ENSP00000426501.1	B4DT06
XYLT2	ENST00000509778.1 linkuse as main transcript	c.121G>A	p.Asp41Asn	missense_variant	2/2	3		ENSP00000425511.1	D6RCT0

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1540

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00292

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00927

AC:

1626

AN:

175480

Hom.:

AF XY:

0.00958

AC XY:

898

AN XY:

93782

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00549

Gnomad ASJ exome

AF:

0.00342

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00295

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0151

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0138

AC:

19587

AN:

1414544

Hom.:

169

Cov.:

AF XY:

0.0136

AC XY:

9480

AN XY:

699316

show subpopulations

Gnomad4 AFR exome

AF:

0.00250

Gnomad4 AMR exome

AF:

0.00714

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00300

Gnomad4 FIN exome

AF:

0.0129

Gnomad4 NFE exome

AF:

0.0162

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0101

AC:

1541

AN:

152272

Hom.:

Cov.:

AF XY:

0.00945

AC XY:

704

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0101

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0184

AC:

ESP6500AA

AF:

0.00364

AC:

ESP6500EA

AF:

0.0137

AC:

118

ExAC

AF:

0.00654

AC:

777

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Osteogenesis imperfecta

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 11, 2022

- -

XYLT2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 19, 2019

This variant is classified as 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

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.065

T;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.051

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

D;D;D

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

N;D;N

REVEL

Benign

0.14

Sift

Benign

0.20

T;D;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0050

B;.;.

Vest4

0.22

MVP

0.31

MPC

0.43

ClinPred

0.023

GERP RS

4.4

Varity_R

0.092

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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