Variant chrX-132628308-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001394073.1(HS6ST2):c.1853C>T(p.Pro618Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,165,349 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000018 ( 0 hom. 5 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.43

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.074448764).

BP6

Variant X-132628308-G-A is Benign according to our data. Variant chrX-132628308-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1285356.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 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.1853C>T	p.Pro618Leu	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.1853C>T	p.Pro618Leu	missense_variant	5/5	5	NM_001394073.1	ENSP00000359870.3		Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.00000901

AC:

AN:

110952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33186

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000343

AC:

AN:

116744

Hom.:

AF XY:

0.0000486

AC XY:

AN XY:

41122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000121

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000659

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1054397

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

344813

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000368

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000220

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000901

AC:

AN:

110952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Paganini-Miozzo syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0030

DANN

Benign

0.52

DEOGEN2

Benign

0.034

T;.;.;T

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.51

.;.;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.074

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;.;.;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.56

N;N;.;.

REVEL

Benign

0.11

Sift

Benign

0.22

T;T;.;.

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

0.0010

B;.;.;B

Vest4

0.034

MutPred

0.12

Gain of helix (P = 0.005);.;.;Gain of helix (P = 0.005);

MVP

0.84

MPC

0.62

ClinPred

0.018

GERP RS

-3.1

Varity_R

0.044

gMVP

0.49

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