rs886568

Positions:

• chr17-50355720-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022167.4(XYLT2):​c.1089-61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,596,328 control chromosomes in the GnomAD database, including 169,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16824 hom., cov: 32)
  • Exomes 𝑓: 0.45 (152996 hom.)
• Consequence: XYLT2 NM_022167.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.530

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-50355720-G-A is Benign according to our data. Variant chr17-50355720-G-A is described in ClinVar as [Benign]. Clinvar id is 1251360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLT2	NM_022167.4	c.1089-61G>A		intron_variant		ENST00000017003.7	NP_071450.2
XYLT2	XM_005257572.5	c.993-61G>A		intron_variant			XP_005257629.1
XYLT2	XM_047436522.1	c.498-61G>A		intron_variant			XP_047292478.1
XYLT2	NR_110010.2	n.1104-61G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT2	ENST00000017003.7	c.1089-61G>A		intron_variant		1	NM_022167.4	ENSP00000017003.2
XYLT2	ENST00000376550.7	n.1089-61G>A		intron_variant		1		ENSP00000365733.3
XYLT2	ENST00000507602.5	c.1089-61G>A		intron_variant		2		ENSP00000426501.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70035 AN: 151886 Hom.: 16787 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.453 AC: 654171 AN: 1444322 Hom.: 152996 Cov.: 29 AF XY: 0.448 AC XY: 321322 AN XY: 717998

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.603

Gnomad4 ASJ exome AF: 0.435

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.311

Gnomad4 FIN exome AF: 0.407

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.461 AC: 70128 AN: 152006 Hom.: 16824 Cov.: 32 AF XY: 0.454 AC XY: 33751 AN XY: 74286

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.487

Alfa AF: 0.471 Hom.: 2695

Bravo AF: 0.478

Asia WGS AF: 0.290 AC: 1013 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs886568; hg19: chr17-48433081;