2-106122169-C-T

Variant names:

• chr2-106122169-C-T
• rs2167531
• NM_001253875.2:c.759+801G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001253875.2(UXS1):​c.759+801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,086 control chromosomes in the GnomAD database, including 26,432 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26432 hom., cov: 33)
• Consequence: UXS1 NM_001253875.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

Genes affected

UXS1 (HGNC:17729): (UDP-glucuronate decarboxylase 1) This gene encodes an enzyme found in the perinuclear Golgi which catalyzes the synthesis of UDP-xylose used in glycosaminoglycan (GAG) synthesis on proteoglycans. The GAG chains are covalently attached to proteoglycans which participate in signaling pathways during development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UXS1	NM_001253875.2	c.759+801G>A		intron_variant	Intron 9 of 14	ENST00000283148.12	NP_001240804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UXS1	ENST00000283148.12	c.759+801G>A		intron_variant	Intron 9 of 14	2	NM_001253875.2	ENSP00000283148.7

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89232 AN: 151968 Hom.: 26422 Cov.: 33

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.600

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.587 AC: 89278 AN: 152086 Hom.: 26432 Cov.: 33 AF XY: 0.589 AC XY: 43785 AN XY: 74350

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.601

Alfa AF: 0.610 Hom.: 13905

Bravo AF: 0.575

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.42

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: rs2167531; hg19: chr2-106738625;