Variant X-132628513-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. Variant has been reported in ClinVar as Likely benign (★).

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 criteria provided, single submitter B:1

Conservation

PhyloP100: 4.75

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 made for transcript

Verdict is Benign. Variant got -10 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 id is 3038566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd at 46 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS6ST2	NM_001394073.1 linkuse as main transcript	c.1648G>T	p.Ala550Ser	missense_variant	5/5	ENST00000370833.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS6ST2	ENST00000370833.7 linkuse as main transcript	c.1648G>T	p.Ala550Ser	missense_variant	5/5	5	NM_001394073.1		Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

157

AN:

111057

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

AN XY:

33245

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

GnomAD3 exomes

AF:

0.00151

AC:

273

AN:

180719

Hom.:

AF XY:

0.00152

AC XY:

102

AN XY:

67063

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 SAS exome

AF:

0.000315

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

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000227

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000240

Gnomad4 FIN exome

AF:

0.00247

Gnomad4 NFE exome

AF:

0.00266

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.00141

AC:

157

AN:

111108

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

AN XY:

33306

show subpopulations

Gnomad4 AFR

AF:

0.000393

Gnomad4 AMR

AF:

0.0000958

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000768

Gnomad4 FIN

AF:

0.00118

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.000665

Alfa

AF:

0.00232

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HS6ST2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

This variant is classified as likely 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

0.14

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.066

T;.;.;T

FATHMM_MKL

Pathogenic

0.99

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.81

L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

0.20

N;N;.;.

REVEL

Benign

0.28

Sift

Benign

0.078

T;T;.;.

Sift4G

Benign

0.22

T;T;T;T

Polyphen

1.0

D;.;.;D

Vest4

0.26

MVP

0.77

MPC

0.70

ClinPred

0.024

GERP RS

6.0

Varity_R

0.24

gMVP

0.56

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