rs5975352

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1	c.948-55303T>C		intron_variant	Intron 2 of 4	ENST00000370833.7	NP_001381002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST2	ENST00000370833.7	c.948-55303T>C		intron_variant	Intron 2 of 4	5	NM_001394073.1	ENSP00000359870.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 16479 AN: 111319 Hom.: 1005 Cov.: 23 AF XY: 0.138 AC XY: 4631 AN XY: 33559

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0957

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.154

Alfa AF: 0.154 Hom.: 1653

Bravo AF: 0.144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.4
DANN	Benign	0.64

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: rs5975352; hg19: chrX-131897825;