X-132628630-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001394073.1(HS6ST2):c.1531G>A(p.Glu511Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,209,569 control chromosomes in the GnomAD database, including 166 homozygotes. There are 6,935 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 5 hom., 363 hem., cov: 23)

Exomes 𝑓: 0.019 ( 161 hom. 6572 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.74

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030495226).

BP6

Variant X-132628630-C-T is Benign according to our data. Variant chrX-132628630-C-T is described in ClinVar as [Benign]. Clinvar id is 3037872.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-132628630-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.012 (1336/111669) while in subpopulation NFE AF = 0.0197 (1046/53153). AF 95% confidence interval is 0.0187. There are 5 homozygotes in GnomAd4. There are 363 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1 link	c.1531G>A	p.Glu511Lys	missense_variant	Exon 5 of 5	ENST00000370833.7	NP_001381002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST2	ENST00000370833.7 link	c.1531G>A	p.Glu511Lys	missense_variant	Exon 5 of 5	5	NM_001394073.1	ENSP00000359870.3		Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1335

AN:

111616

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00323

Gnomad AMI

AF:

0.00585

Gnomad AMR

AF:

0.00534

Gnomad ASJ

AF:

0.00904

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00265

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.0197

Gnomad OTH

AF:

0.00672

GnomAD2 exomes

AF:

0.0119

AC:

2153

AN:

181075

AF XY:

0.0120

show subpopulations

Gnomad AFR exome

AF:

0.00266

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.00925

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0184

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.0188

AC:

20587

AN:

1097900

Hom.:

161

Cov.:

AF XY:

0.0181

AC XY:

6572

AN XY:

363370

show subpopulations

Gnomad4 AFR exome

AF:

0.00220

AC:

AN:

26399

Gnomad4 AMR exome

AF:

0.00474

AC:

167

AN:

35207

Gnomad4 ASJ exome

AF:

0.0103

AC:

199

AN:

19385

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

30192

Gnomad4 SAS exome

AF:

0.00242

AC:

131

AN:

54145

Gnomad4 FIN exome

AF:

0.0176

AC:

715

AN:

40515

Gnomad4 NFE exome

AF:

0.0221

AC:

18624

AN:

841852

Gnomad4 Remaining exome

AF:

0.0148

AC:

684

AN:

46072

Heterozygous variant carriers

843

1686

2530

3373

4216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

744

1488

2232

2976

3720

<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:

0.0120

AC:

1336

AN:

111669

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

363

AN XY:

33859

show subpopulations

Gnomad4 AFR

AF:

0.00322

AC:

0.00321899

AN:

0.00321899

Gnomad4 AMR

AF:

0.00533

AC:

0.00533486

AN:

0.00533486

Gnomad4 ASJ

AF:

0.00904

AC:

0.00903955

AN:

0.00903955

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00265

AC:

0.00265453

AN:

0.00265453

Gnomad4 FIN

AF:

0.0148

AC:

0.0148087

AN:

0.0148087

Gnomad4 NFE

AF:

0.0197

AC:

0.019679

AN:

0.019679

Gnomad4 OTH

AF:

0.00664

AC:

0.0066357

AN:

0.0066357

Heterozygous variant carriers

141

188

235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0169

Hom.:

783

Bravo

AF:

0.0109

TwinsUK

AF:

0.0291

AC:

108

ALSPAC

AF:

0.0263

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0173

AC:

111

ExAC

AF:

0.0114

AC:

1379

EpiCase

AF:

0.0185

EpiControl

AF:

0.0177

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HS6ST2-related disorder

Benign:1

Apr 30, 2024

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;.;.;T

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

.;.;T;T

MetaRNN

Benign

0.0030

T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.7

L;.;.;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

N;N;.;.

REVEL

Benign

0.17

Sift

Benign

0.10

T;T;.;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.32

B;.;.;B

Vest4

0.12

MPC

0.71

ClinPred

0.011

GERP RS

5.1

Varity_R

0.37

gMVP

0.39

Mutation Taster

=97/3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over