17-50346373-G-C

Variant names:

• chr17-50346373-G-C
• rs184856639
• NM_022167.4:c.135+98G>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_022167.4(XYLT2):​c.135+98G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 984,526 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (930 hom., cov: 32)
  • Exomes 𝑓: 0.019 (506 hom.)
• Consequence: XYLT2 NM_022167.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.16
• Publications: 0 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), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 17-50346373-G-C is Benign according to our data. Variant chr17-50346373-G-C is described in ClinVar as Benign. ClinVar VariationId is 1251286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 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.135+98G>C		intron	N/A	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.150+98G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT2	ENST00000017003.7	TSL:1 MANE Select	c.135+98G>C		intron	N/A	ENSP00000017003.2	Q9H1B5-1
	XYLT2	ENST00000376550.7	TSL:1	n.135+98G>C		intron	N/A	ENSP00000365733.3	A0A0C4DFW8
	XYLT2	ENST00000854775.1		c.135+98G>C		intron	N/A	ENSP00000524834.1

Frequencies

GnomAD3 genomes AF: 0.0708 AC: 10639 AN: 150238 Hom.: 930 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.000775

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.00346

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0521

GnomAD4 exome AF: 0.0190 AC: 15809 AN: 834180 Hom.: 506 AF XY: 0.0187 AC XY: 7227 AN XY: 385940

African (AFR) AF: 0.222 AC: 3502 AN: 15772

American (AMR) AF: 0.0197 AC: 23 AN: 1168

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 64 AN: 5224

East Asian (EAS) AF: 0.00 AC: 0 AN: 3754

South Asian (SAS) AF: 0.0469 AC: 809 AN: 17256

European-Finnish (FIN) AF: 0.00119 AC: 1 AN: 840

Middle Eastern (MID) AF: 0.0526 AC: 86 AN: 1636

European-Non Finnish (NFE) AF: 0.0140 AC: 10633 AN: 761132

Other (OTH) AF: 0.0252 AC: 691 AN: 27398

GnomAD4 genome AF: 0.0709 AC: 10653 AN: 150346 Hom.: 930 Cov.: 32 AF XY: 0.0691 AC XY: 5074 AN XY: 73464

African (AFR) AF: 0.203 AC: 8369 AN: 41214

American (AMR) AF: 0.0423 AC: 640 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 73 AN: 3462

East Asian (EAS) AF: 0.000778 AC: 4 AN: 5144

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4824

European-Finnish (FIN) AF: 0.00346 AC: 34 AN: 9832

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0178 AC: 1198 AN: 67456

Other (OTH) AF: 0.0511 AC: 107 AN: 2094

Alfa AF: 0.00499 Hom.: 2

Bravo AF: 0.0782

Asia WGS AF: 0.0190 AC: 69 AN: 3462

ClinVar

ClinVar submissions as Germline

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	-0.41
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		1.2
PromoterAI		-0.040	Neutral
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs184856639; hg19: chr17-48423734;