rs5933220

Variant names:

• chrX-132855005-T-C
• rs5933220
• NM_001394073.1:c.947+101803A>G

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+101803A>G 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 0.53 (11980 hom., 17159 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: HS6ST2 NM_001394073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 2 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=-0.91).

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.947+101803A>G		intron	N/A	NP_001381002.1	Q96MM7-4
	HS6ST2	NM_001077188.2		c.947+101803A>G		intron	N/A	NP_001070656.1	Q96MM7-4
	HS6ST2	NM_001394074.1		c.947+101803A>G		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.947+101803A>G		intron	N/A	ENSP00000359870.3	Q96MM7-4
	HS6ST2	ENST00000406696.5	TSL:1	c.509+101803A>G		intron	N/A	ENSP00000384013.5	Q96MM7-3
	HS6ST2	ENST00000521489.5	TSL:5	c.947+101803A>G		intron	N/A	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes AF: 0.535 AC: 59248 AN: 110791 Hom.: 11979 Cov.: 23

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.509

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: 0.535 AC: 59282 AN: 110847 Hom.: 11980 Cov.: 23 AF XY: 0.518 AC XY: 17159 AN XY: 33099

African (AFR) AF: 0.692 AC: 21053 AN: 30402

American (AMR) AF: 0.348 AC: 3657 AN: 10510

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1182 AN: 2636

East Asian (EAS) AF: 0.369 AC: 1288 AN: 3490

South Asian (SAS) AF: 0.428 AC: 1133 AN: 2650

European-Finnish (FIN) AF: 0.517 AC: 3038 AN: 5878

Middle Eastern (MID) AF: 0.553 AC: 119 AN: 215

European-Non Finnish (NFE) AF: 0.506 AC: 26732 AN: 52882

Other (OTH) AF: 0.508 AC: 767 AN: 1509

Alfa AF: 0.389 Hom.: 2799

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.6
DANN	Benign	0.79
PhyloP100		0.25
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: rs5933220; hg19: chrX-131989033;