chr17-50346373-G-C

Position:

• chr17-50346373-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLT2	NM_022167.4	c.135+98G>C		intron_variant		ENST00000017003.7	NP_071450.2
XYLT2	NR_110010.2	n.150+98G>C		intron_variant
XYLT2	XM_005257572.5	c.-523G>C		upstream_gene_variant			XP_005257629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT2	ENST00000017003.7	c.135+98G>C		intron_variant		1	NM_022167.4	ENSP00000017003.2
XYLT2	ENST00000376550.7	n.135+98G>C		intron_variant		1		ENSP00000365733.3
XYLT2	ENST00000507602.5	c.135+98G>C		intron_variant		2		ENSP00000426501.1
XYLT2	ENST00000509778.1	c.90+143G>C		intron_variant		3		ENSP00000425511.1

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

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0197

Gnomad4 ASJ exome AF: 0.0123

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0469

Gnomad4 FIN exome AF: 0.00119

Gnomad4 NFE exome AF: 0.0140

Gnomad4 OTH exome AF: 0.0252

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

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0211

Gnomad4 EAS AF: 0.000778

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.00346

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.00499 Hom.: 2

Bravo AF: 0.0782

Asia WGS AF: 0.0190 AC: 69 AN: 3462

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 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs184856639; hg19: chr17-48423734;