X-132798388-T-G

Variant names:

• chrX-132798388-T-G
• rs17317147
• NM_001394073.1:c.948-89894A>C

Variant summary

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

The NM_001394073.1(HS6ST2):​c.948-89894A>C 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 0.55 (12581 hom., 17006 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HS6ST2 NM_001394073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	NM_001394073.1	MANE Select	c.948-89894A>C		intron	N/A	NP_001381002.1	Q96MM7-4
	HS6ST2	NM_001077188.2		c.948-89894A>C		intron	N/A	NP_001070656.1	Q96MM7-4
	HS6ST2	NM_001394074.1		c.947+158420A>C		intron	N/A	NP_001381003.1	Q96MM7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	ENST00000370833.7	TSL:5 MANE Select	c.948-89894A>C		intron	N/A	ENSP00000359870.3	Q96MM7-4
	HS6ST2	ENST00000406696.5	TSL:1	c.510-89894A>C		intron	N/A	ENSP00000384013.5	Q96MM7-3
	HS6ST2	ENST00000521489.5	TSL:5	c.948-89894A>C		intron	N/A	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 60031 AN: 109672 Hom.: 12578 Cov.: 22

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.568

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.525

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: 0.547 AC: 60069 AN: 109724 Hom.: 12581 Cov.: 22 AF XY: 0.531 AC XY: 17006 AN XY: 31998

African (AFR) AF: 0.724 AC: 21861 AN: 30195

American (AMR) AF: 0.364 AC: 3740 AN: 10288

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1289 AN: 2616

East Asian (EAS) AF: 0.423 AC: 1450 AN: 3431

South Asian (SAS) AF: 0.499 AC: 1261 AN: 2527

European-Finnish (FIN) AF: 0.489 AC: 2813 AN: 5747

Middle Eastern (MID) AF: 0.565 AC: 122 AN: 216

European-Non Finnish (NFE) AF: 0.503 AC: 26424 AN: 52558

Other (OTH) AF: 0.524 AC: 775 AN: 1480

Alfa AF: 0.444 Hom.: 4159

Bravo AF: 0.544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.75
PhyloP100		0.0060
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: rs17317147; hg19: chrX-131932416;