rs886568

Variant names:

• chr17-50355720-G-A
• rs886568
• NM_022167.4:c.1089-61G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.1089-61G>A		intron	N/A	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.1104-61G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT2	ENST00000017003.7	TSL:1 MANE Select	c.1089-61G>A		intron	N/A	ENSP00000017003.2	Q9H1B5-1
	XYLT2	ENST00000376550.7	TSL:1	n.1089-61G>A		intron	N/A	ENSP00000365733.3	A0A0C4DFW8
	XYLT2	ENST00000854775.1		c.1089-61G>A		intron	N/A	ENSP00000524834.1

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

African (AFR) AF: 0.509 AC: 16804 AN: 33036

American (AMR) AF: 0.603 AC: 26239 AN: 43542

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 11221 AN: 25810

East Asian (EAS) AF: 0.114 AC: 4484 AN: 39434

South Asian (SAS) AF: 0.311 AC: 26554 AN: 85388

European-Finnish (FIN) AF: 0.407 AC: 21151 AN: 51918

Middle Eastern (MID) AF: 0.466 AC: 2657 AN: 5698

European-Non Finnish (NFE) AF: 0.472 AC: 518784 AN: 1099794

Other (OTH) AF: 0.440 AC: 26277 AN: 59702

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

African (AFR) AF: 0.504 AC: 20861 AN: 41420

American (AMR) AF: 0.560 AC: 8560 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3468

East Asian (EAS) AF: 0.118 AC: 609 AN: 5178

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4816

European-Finnish (FIN) AF: 0.397 AC: 4197 AN: 10562

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31471 AN: 67952

Other (OTH) AF: 0.487 AC: 1031 AN: 2116

Alfa AF: 0.471 Hom.: 2695

Bravo AF: 0.478

Asia WGS AF: 0.290 AC: 1013 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.59
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs886568; hg19: chr17-48433081;