NM_001394073.1:c.947+92985G>A

Variant names:

• chrX-132863823-C-T
• rs17324216
• NM_001394073.1:c.947+92985G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394073.1(HS6ST2):​c.947+92985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 111,093 control chromosomes in the GnomAD database, including 909 homozygotes. There are 4,399 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 0.14 (909 hom., 4399 hem., cov: 22)
• Consequence: HS6ST2 NM_001394073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	NM_001394073.1	MANE Select	c.947+92985G>A		intron	N/A	NP_001381002.1
	HS6ST2	NM_001077188.2		c.947+92985G>A		intron	N/A	NP_001070656.1
	HS6ST2	NM_001394074.1		c.947+92985G>A		intron	N/A	NP_001381003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	ENST00000370833.7	TSL:5 MANE Select	c.947+92985G>A		intron	N/A	ENSP00000359870.3
	HS6ST2	ENST00000406696.5	TSL:1	c.509+92985G>A		intron	N/A	ENSP00000384013.5
	HS6ST2	ENST00000521489.5	TSL:5	c.947+92985G>A		intron	N/A	ENSP00000429473.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 15290 AN: 111042 Hom.: 911 Cov.: 22

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.0751

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.246

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.138 AC: 15282 AN: 111093 Hom.: 909 Cov.: 22 AF XY: 0.132 AC XY: 4399 AN XY: 33357

African (AFR) AF: 0.0810 AC: 2481 AN: 30617

American (AMR) AF: 0.106 AC: 1102 AN: 10418

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 444 AN: 2631

East Asian (EAS) AF: 0.337 AC: 1179 AN: 3494

South Asian (SAS) AF: 0.270 AC: 710 AN: 2629

European-Finnish (FIN) AF: 0.106 AC: 635 AN: 5983

Middle Eastern (MID) AF: 0.242 AC: 52 AN: 215

European-Non Finnish (NFE) AF: 0.159 AC: 8406 AN: 52921

Other (OTH) AF: 0.147 AC: 222 AN: 1506

Alfa AF: 0.158 Hom.: 10745

Bravo AF: 0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.72
PhyloP100		1.2
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: rs17324216; hg19: chrX-131997851;