chr17-50353671-G-A

Position:

• chr17-50353671-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022167.4(XYLT2):​c.177G>A​(p.Glu59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,566,316 control chromosomes in the GnomAD database, including 40,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3036 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37440 hom.)
• Consequence: XYLT2 NM_022167.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.132

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 17-50353671-G-A is Benign according to our data. Variant chr17-50353671-G-A is described in ClinVar as [Benign]. Clinvar id is 1243238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50353671-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.132 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLT2	NM_022167.4	c.177G>A	p.Glu59=	synonymous_variant	2/11	ENST00000017003.7
XYLT2	XM_005257572.5	c.81G>A	p.Glu27=	synonymous_variant	2/11
XYLT2	XM_047436522.1	c.-415G>A		5_prime_UTR_variant	2/11
XYLT2	NR_110010.2	n.192G>A		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLT2	ENST00000017003.7	c.177G>A	p.Glu59=	synonymous_variant	2/11	1	NM_022167.4	P1
XYLT2	ENST00000376550.7	c.177G>A	p.Glu59=	synonymous_variant, NMD_transcript_variant	2/10	1
XYLT2	ENST00000507602.5	c.177G>A	p.Glu59=	synonymous_variant	2/10	2
XYLT2	ENST00000509778.1	c.132G>A	p.Glu44=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27649 AN: 152024 Hom.: 3035 Cov.: 33

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0844

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.181

GnomAD3 exomes AF: 0.201 AC: 35346 AN: 175956 Hom.: 4108 AF XY: 0.195 AC XY: 18372 AN XY: 94042

Gnomad AFR exome AF: 0.0744

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0699

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.233

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.224 AC: 316400 AN: 1414174 Hom.: 37440 Cov.: 36 AF XY: 0.221 AC XY: 154202 AN XY: 699042

Gnomad4 AFR exome AF: 0.0695

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.0824

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.182 AC: 27651 AN: 152142 Hom.: 3036 Cov.: 33 AF XY: 0.181 AC XY: 13483 AN XY: 74364

Gnomad4 AFR AF: 0.0756

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.179

Alfa AF: 0.211 Hom.: 1807

Bravo AF: 0.174

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 14, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Spondylo-ocular syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.7
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs739990; hg19: chr17-48431032; COSMIC: COSV50024160; COSMIC: COSV50024160;