17-50353603-A-C

Variant names:

• chr17-50353603-A-C
• rs739991
• NM_022167.4:c.136-27A>C

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.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
• Publications: 3 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 -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 VariationId 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.

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.136-27A>C		intron	N/A	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.151-27A>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.136-27A>C		intron	N/A	ENSP00000017003.2	Q9H1B5-1
	XYLT2	ENST00000376550.7	TSL:1	n.136-27A>C		intron	N/A	ENSP00000365733.3	A0A0C4DFW8
	XYLT2	ENST00000854775.1		c.136-27A>C		intron	N/A	ENSP00000524834.1

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

GnomAD2 exomes AF: 0.0112 AC: 1726 AN: 154256 AF XY: 0.00812

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 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

African (AFR) AF: 0.171 AC: 5362 AN: 31416

American (AMR) AF: 0.00876 AC: 294 AN: 33580

Ashkenazi Jewish (ASJ) AF: 0.000162 AC: 4 AN: 24750

East Asian (EAS) AF: 0.00 AC: 0 AN: 36426

South Asian (SAS) AF: 0.000242 AC: 19 AN: 78452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49210

Middle Eastern (MID) AF: 0.00583 AC: 33 AN: 5658

European-Non Finnish (NFE) AF: 0.000110 AC: 119 AN: 1079474

Other (OTH) AF: 0.00921 AC: 533 AN: 57870

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

African (AFR) AF: 0.164 AC: 6830 AN: 41520

American (AMR) AF: 0.0177 AC: 271 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68024

Other (OTH) AF: 0.0251 AC: 53 AN: 2112

Alfa AF: 0.00732 Hom.: 21

Bravo AF: 0.0539

Asia WGS AF: 0.00635 AC: 24 AN: 3478

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	-0.87
CADD	Benign	0.0090
DANN	Benign	0.61
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs739991; hg19: chr17-48430964;