Variant X-132628630-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS6ST2	NM_001394073.1 linkuse as main transcript	c.1531G>A	p.Glu511Lys	missense_variant	5/5	ENST00000370833.7	NP_001381002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS6ST2	ENST00000370833.7 linkuse as main transcript	c.1531G>A	p.Glu511Lys	missense_variant	5/5	5	NM_001394073.1	ENSP00000359870		Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1335

AN:

111616

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

363

AN XY:

33796

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

GnomAD3 exomes

AF:

0.0119

AC:

2153

AN:

181075

Hom.:

AF XY:

0.0120

AC XY:

807

AN XY:

67277

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 SAS exome

AF:

0.00262

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

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00242

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.0221

Gnomad4 OTH exome

AF:

0.0148

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

Gnomad4 AMR

AF:

0.00533

Gnomad4 ASJ

AF:

0.00904

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00265

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.0197

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.0180

Hom.:

778

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 30, 2024

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

MutationTaster

Benign

0.98

D;D;D;D;D

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

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