X-132760716-A-G

Variant names:

• chrX-132760716-A-G
• rs7881124
• NM_001394073.1:c.948-52222T>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.948-52222T>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 0.58 (13928 hom., 17655 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HS6ST2 NM_001394073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794
• Publications: 4 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=-1.0).

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.948-52222T>C		intron	N/A	NP_001381002.1	Q96MM7-4
	HS6ST2	NM_001077188.2		c.948-52222T>C		intron	N/A	NP_001070656.1	Q96MM7-4
	HS6ST2	NM_001394074.1		c.948-131623T>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.948-52222T>C		intron	N/A	ENSP00000359870.3	Q96MM7-4
	HS6ST2	ENST00000406696.5	TSL:1	c.510-52222T>C		intron	N/A	ENSP00000384013.5	Q96MM7-3
	HS6ST2	ENST00000521489.5	TSL:5	c.948-52222T>C		intron	N/A	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 62892 AN: 109414 Hom.: 13926 Cov.: 22

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.558

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: 0.575 AC: 62946 AN: 109469 Hom.: 13928 Cov.: 22 AF XY: 0.556 AC XY: 17655 AN XY: 31759

African (AFR) AF: 0.768 AC: 22973 AN: 29930

American (AMR) AF: 0.378 AC: 3886 AN: 10276

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1381 AN: 2616

East Asian (EAS) AF: 0.452 AC: 1553 AN: 3434

South Asian (SAS) AF: 0.521 AC: 1299 AN: 2494

European-Finnish (FIN) AF: 0.488 AC: 2787 AN: 5709

Middle Eastern (MID) AF: 0.645 AC: 136 AN: 211

European-Non Finnish (NFE) AF: 0.527 AC: 27768 AN: 52641

Other (OTH) AF: 0.556 AC: 827 AN: 1488

Alfa AF: 0.531 Hom.: 34324

Bravo AF: 0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.29
DANN	Benign	0.36
PhyloP100		-0.79
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: rs7881124; hg19: chrX-131894744;