chr17-50346170-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022167.4(XYLT2):c.30G>T(p.Leu10Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,286,504 control chromosomes in the GnomAD database, including 769 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 480 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 289 hom. )

Consequence

XYLT2
NM_022167.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.45

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-50346170-G-T is Benign according to our data. Variant chr17-50346170-G-T is described in ClinVar as [Benign]. Clinvar id is 1277109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XYLT2	NM_022167.4 link	c.30G>T	p.Leu10Leu	synonymous_variant	Exon 1 of 11	ENST00000017003.7	NP_071450.2	Q9H1B5-1B4DT06
XYLT2	NR_110010.2 link	n.45G>T		non_coding_transcript_exon_variant	Exon 1 of 10
XYLT2	XM_005257572.5 link	c.-726G>T		upstream_gene_variant			XP_005257629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
XYLT2	ENST00000017003.7 link	c.30G>T	p.Leu10Leu	synonymous_variant	Exon 1 of 11	1	NM_022167.4	ENSP00000017003.2	Q9H1B5-1
XYLT2	ENST00000376550.7 link	n.30G>T		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000365733.3	A0A0C4DFW8
XYLT2	ENST00000507602.5 link	c.30G>T	p.Leu10Leu	synonymous_variant	Exon 1 of 10	2		ENSP00000426501.1	B4DT06
XYLT2	ENST00000509778.1 link	c.30G>T	p.Leu10Leu	synonymous_variant	Exon 1 of 2	3		ENSP00000425511.1	D6RCT0

Frequencies

GnomAD3 genomes

AF:

0.0433

AC:

6410

AN:

147942

Hom.:

482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.000880

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.000331

Gnomad OTH

AF:

0.0216

GnomAD2 exomes

AF:

0.00521

AC:

437

AN:

83880

AF XY:

0.00326

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.00446

Gnomad ASJ exome

AF:

0.000149

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000166

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00348

AC:

3965

AN:

1138454

Hom.:

289

Cov.:

AF XY:

0.00301

AC XY:

1689

AN XY:

560850

show subpopulations

Gnomad4 AFR exome

AF:

0.157

AC:

3432

AN:

21926

Gnomad4 AMR exome

AF:

0.00593

AC:

120

AN:

20250

Gnomad4 ASJ exome

AF:

0.000121

AC:

AN:

16528

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

17230

Gnomad4 SAS exome

AF:

0.000222

AC:

AN:

63136

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

29802

Gnomad4 NFE exome

AF:

0.0000800

AC:

AN:

925046

Gnomad4 Remaining exome

AF:

0.00745

AC:

309

AN:

41458

Heterozygous variant carriers

194

389

583

778

972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.0433

AC:

6412

AN:

148050

Hom.:

480

Cov.:

AF XY:

0.0420

AC XY:

3033

AN XY:

72166

show subpopulations

Gnomad4 AFR

AF:

0.148

AC:

0.148139

AN:

0.148139

Gnomad4 AMR

AF:

0.0161

AC:

0.0161095

AN:

0.0161095

Gnomad4 ASJ

AF:

0.000880

AC:

0.000879765

AN:

0.000879765

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000621

AC:

0.000621375

AN:

0.000621375

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000331

AC:

0.000331465

AN:

0.000331465

Gnomad4 OTH

AF:

0.0213

AC:

0.0213385

AN:

0.0213385

Heterozygous variant carriers

281

562

843

1124

1405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0271

Hom.:

Bravo

AF:

0.0478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Osteogenesis imperfecta

Benign:1

Aug 13, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Spondylo-ocular syndrome

Benign:1

Dec 05, 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

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism (auto)

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