chrX-132628513-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001394073.1(HS6ST2):c.1648G>T(p.Ala550Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,209,099 control chromosomes in the GnomAD database, including 5 homozygotes. There are 815 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 46 hem., cov: 22)

Exomes 𝑓: 0.0022 ( 5 hom. 769 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.75

Publications

4 publications found

Variant links:

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

HS6ST2 links:

ENSG00000296977 (HGNC:):

ENSG00000296977 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013007343).

BP6

Variant X-132628513-C-A is Benign according to our data. Variant chrX-132628513-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3038566.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 46 Unknown,XL gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS6ST2	NM_001394073.1	MANE Select	c.1648G>T	p.Ala550Ser	missense	Exon 5 of 5	NP_001381002.1	Q96MM7-4
HS6ST2	NM_001077188.2		c.1648G>T	p.Ala550Ser	missense	Exon 6 of 6	NP_001070656.1	Q96MM7-4
HS6ST2	NM_001394074.1		c.1528G>T	p.Ala510Ser	missense	Exon 3 of 3	NP_001381003.1	Q96MM7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS6ST2	ENST00000370833.7	TSL:5 MANE Select	c.1648G>T	p.Ala550Ser	missense	Exon 5 of 5	ENSP00000359870.3	Q96MM7-4
HS6ST2	ENST00000406696.5	TSL:1	c.1210G>T	p.Ala404Ser	missense	Exon 5 of 5	ENSP00000384013.5	Q96MM7-3
HS6ST2	ENST00000521489.5	TSL:5	c.1648G>T	p.Ala550Ser	missense	Exon 6 of 6	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

157

AN:

111057

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000394

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000959

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000766

Gnomad FIN

AF:

0.00118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.000673

GnomAD2 exomes

AF:

0.00151

AC:

273

AN:

180719

AF XY:

0.00152

show subpopulations

Gnomad AFR exome

AF:

0.000404

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.000450

GnomAD4 exome

AF:

0.00223

AC:

2444

AN:

1097991

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

769

AN XY:

363459

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

26403

American (AMR)

AF:

0.000227

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.000103

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30186

South Asian (SAS)

AF:

0.000240

AC:

AN:

54144

European-Finnish (FIN)

AF:

0.00247

AC:

100

AN:

40480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00266

AC:

2241

AN:

841976

Other (OTH)

AF:

0.00165

AC:

AN:

46075

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00141

AC:

157

AN:

111108

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

AN XY:

33306

show subpopulations

African (AFR)

AF:

0.000393

AC:

AN:

30516

American (AMR)

AF:

0.0000958

AC:

AN:

10436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2635

East Asian (EAS)

AF:

0.00

AC:

AN:

3528

South Asian (SAS)

AF:

0.000768

AC:

AN:

2605

European-Finnish (FIN)

AF:

0.00118

AC:

AN:

5925

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00253

AC:

134

AN:

53060

Other (OTH)

AF:

0.000665

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.00153

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00381

AC:

ESP6500AA

AF:

0.00119

AC:

ESP6500EA

AF:

0.00216

AC:

ExAC

AF:

0.00151

AC:

183

EpiCase

AF:

0.00316

EpiControl

AF:

0.00196

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

HS6ST2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.81

PhyloP100

4.8

PrimateAI

Benign

0.46

PROVEAN

Benign

0.20

REVEL

Benign

0.28

Sift

Benign

0.078

Sift4G

Benign

0.22

Polyphen

1.0

Vest4

0.26

MVP

0.77

MPC

0.70

ClinPred

0.024

GERP RS

6.0

Varity_R

0.24

gMVP

0.56

Mutation Taster

=65/35

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over