X-132877663-G-T

Variant names:

• chrX-132877663-G-T
• rs5933229
• NM_001394073.1:c.947+79145C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394073.1(HS6ST2):​c.947+79145C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.54 (12060 hom., 16737 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HS6ST2 NM_001394073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1	c.947+79145C>A		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.947+79145C>A		intron_variant	Intron 2 of 4	5	NM_001394073.1	ENSP00000359870.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 58931 AN: 109681 Hom.: 12059 Cov.: 22

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.575

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.517

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.537 AC: 58962 AN: 109731 Hom.: 12060 Cov.: 22 AF XY: 0.523 AC XY: 16737 AN XY: 32025

African (AFR) AF: 0.699 AC: 21084 AN: 30151

American (AMR) AF: 0.348 AC: 3570 AN: 10258

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1174 AN: 2627

East Asian (EAS) AF: 0.367 AC: 1253 AN: 3417

South Asian (SAS) AF: 0.429 AC: 1096 AN: 2557

European-Finnish (FIN) AF: 0.522 AC: 2969 AN: 5687

Middle Eastern (MID) AF: 0.566 AC: 120 AN: 212

European-Non Finnish (NFE) AF: 0.505 AC: 26614 AN: 52664

Other (OTH) AF: 0.515 AC: 764 AN: 1483

Alfa AF: 0.541 Hom.: 4670

Bravo AF: 0.531

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.050
DANN	Benign	0.50
PhyloP100		-1.1
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: rs5933229; hg19: chrX-132011691;