2-106122169-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

UXS1 Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001253875.2. 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
	UXS1	NM_001253875.2	MANE Select	c.759+801G>A		intron	N/A	NP_001240804.1	Q8NBZ7-2
	UXS1	NM_025076.5		c.744+801G>A		intron	N/A	NP_079352.2
	UXS1	NM_001377504.1		c.759+801G>A		intron	N/A	NP_001364433.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UXS1	ENST00000283148.12	TSL:2 MANE Select	c.759+801G>A		intron	N/A	ENSP00000283148.7	Q8NBZ7-2
	UXS1	ENST00000409501.7	TSL:1	c.744+801G>A		intron	N/A	ENSP00000387019.3	Q8NBZ7-1
	UXS1	ENST00000409032.5	TSL:1	c.240+801G>A		intron	N/A	ENSP00000387096.1	Q8NBZ7-3

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

African (AFR) AF: 0.515 AC: 21371 AN: 41460

American (AMR) AF: 0.567 AC: 8663 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2997 AN: 5172

South Asian (SAS) AF: 0.642 AC: 3102 AN: 4830

European-Finnish (FIN) AF: 0.613 AC: 6479 AN: 10576

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42657 AN: 67978

Other (OTH) AF: 0.601 AC: 1270 AN: 2112

Alfa AF: 0.609 Hom.: 15440

Bravo AF: 0.575

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.42
PhyloP100		0.084
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2167531; hg19: chr2-106738625;