17-50353603-A-C

Position:

• chr17-50353603-A-C

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.136-27A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00875 in 1,549,098 control chromosomes in the GnomAD database, including 1,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (589 hom., cov: 32)
  • Exomes 𝑓: 0.0046 (491 hom.)
• Consequence: XYLT2 NM_022167.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 17-50353603-A-C is Benign according to our data. Variant chr17-50353603-A-C is described in ClinVar as [Benign]. Clinvar id is 1261063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XYLT2	NM_022167.4	c.136-27A>C		intron_variant		ENST00000017003.7	NP_071450.2
XYLT2	XM_005257572.5	c.40-27A>C		intron_variant			XP_005257629.1
XYLT2	XM_047436522.1	c.-456-27A>C		intron_variant			XP_047292478.1
XYLT2	NR_110010.2	n.151-27A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XYLT2	ENST00000017003.7	c.136-27A>C		intron_variant		1	NM_022167.4	ENSP00000017003.2
XYLT2	ENST00000376550.7	n.136-27A>C		intron_variant		1		ENSP00000365733.3
XYLT2	ENST00000507602.5	c.136-27A>C		intron_variant		2		ENSP00000426501.1
XYLT2	ENST00000509778.1	c.91-27A>C		intron_variant		3		ENSP00000425511.1

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7184 AN: 152144 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0254

GnomAD3 exomes AF: 0.0112 AC: 1726 AN: 154256 Hom.: 127 AF XY: 0.00812 AC XY: 671 AN XY: 82594

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.00742

Gnomad ASJ exome AF: 0.000371

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000908

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00651

GnomAD4 exome AF: 0.00456 AC: 6364 AN: 1396836 Hom.: 491 Cov.: 31 AF XY: 0.00398 AC XY: 2742 AN XY: 689594

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.00876

Gnomad4 ASJ exome AF: 0.000162

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000242

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.00921

GnomAD4 genome AF: 0.0472 AC: 7189 AN: 152262 Hom.: 589 Cov.: 32 AF XY: 0.0456 AC XY: 3392 AN XY: 74454

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.00364 Hom.: 6

Bravo AF: 0.0539

Asia WGS AF: 0.00635 AC: 24 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 23, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0090
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs739991; hg19: chr17-48430964;