rs5975352

Variant names:

• chrX-132763797-A-G
• rs5975352
• NM_001394073.1:c.948-55303T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394073.1(HS6ST2):​c.948-55303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 111,369 control chromosomes in the GnomAD database, including 1,004 homozygotes. There are 4,631 hemizygotes in GnomAD. 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 0.15 (1004 hom., 4631 hem., cov: 23)
• Consequence: HS6ST2 NM_001394073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 1 publications found

Genes affected

HS6ST2 (HGNC:19133): (heparan sulfate 6-O-sulfotransferase 2) Heparan sulfate proteoglycans are ubiquitous components of the cell surface, extracellular matrix, and basement membranes, and interact with various ligands to influence cell growth, differentiation, adhesion, and migration. This gene encodes a member of the heparan sulfate (HS) sulfotransferase gene family, which catalyze the transfer of sulfate to HS. Different family members and isoforms are thought to synthesize heparan sulfates with tissue-specific structures and functions. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HS6ST2 Gene-Disease associations (from GenCC):

• Paganini-Miozzo syndrome

  Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394073.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	NM_001394073.1	MANE Select	c.948-55303T>C		intron	N/A	NP_001381002.1
	HS6ST2	NM_001077188.2		c.948-55303T>C		intron	N/A	NP_001070656.1
	HS6ST2	NM_001394074.1		c.948-134704T>C		intron	N/A	NP_001381003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	ENST00000370833.7	TSL:5 MANE Select	c.948-55303T>C		intron	N/A	ENSP00000359870.3
	HS6ST2	ENST00000406696.5	TSL:1	c.510-55303T>C		intron	N/A	ENSP00000384013.5
	HS6ST2	ENST00000521489.5	TSL:5	c.948-55303T>C		intron	N/A	ENSP00000429473.1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 16479 AN: 111319 Hom.: 1005 Cov.: 23

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0733

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.148 AC: 16479 AN: 111369 Hom.: 1004 Cov.: 23 AF XY: 0.138 AC XY: 4631 AN XY: 33619

African (AFR) AF: 0.139 AC: 4252 AN: 30678

American (AMR) AF: 0.0957 AC: 1005 AN: 10502

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 446 AN: 2632

East Asian (EAS) AF: 0.287 AC: 1005 AN: 3496

South Asian (SAS) AF: 0.273 AC: 711 AN: 2607

European-Finnish (FIN) AF: 0.105 AC: 630 AN: 5994

Middle Eastern (MID) AF: 0.168 AC: 36 AN: 214

European-Non Finnish (NFE) AF: 0.153 AC: 8110 AN: 53046

Other (OTH) AF: 0.154 AC: 234 AN: 1518

Alfa AF: 0.154 Hom.: 1653

Bravo AF: 0.144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.4
DANN	Benign	0.64
PhyloP100		1.3
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: rs5975352; hg19: chrX-131897825;