Variant X-132628419-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001394073.1(HS6ST2):c.1742C>A(p.Pro581Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,202,291 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.991

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=0.05521202).

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1 link	c.1742C>A	p.Pro581Gln	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.1742C>A	p.Pro581Gln	missense_variant	Exon 5 of 5	5	NM_001394073.1	ENSP00000359870.3		Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.0000902

AC:

AN:

110904

Hom.:

Cov.:

AF XY:

0.0000906

AC XY:

AN XY:

33130

show subpopulations

Gnomad AFR

AF:

0.000296

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000960

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000232

AC:

AN:

172563

Hom.:

AF XY:

0.00

AC XY:

AN XY:

61365

show subpopulations

Gnomad AFR exome

AF:

0.000167

Gnomad AMR exome

AF:

0.0000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1091387

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357533

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000902

AC:

AN:

110904

Hom.:

Cov.:

AF XY:

0.0000906

AC XY:

AN XY:

33130

show subpopulations

Gnomad4 AFR

AF:

0.000296

Gnomad4 AMR

AF:

0.0000960

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.000305

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.31

DANN

Benign

0.67

DEOGEN2

Benign

0.085

T;.;.;T

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.52

.;.;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

L;.;.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.96

N;N;.;.

REVEL

Benign

0.19

Sift

Benign

0.10

T;T;.;.

Sift4G

Uncertain

0.026

D;D;D;D

Polyphen

0.0

B;.;.;B

Vest4

0.13

MVP

0.67

MPC

0.57

ClinPred

0.0072

GERP RS

-3.0

Varity_R

0.039

gMVP

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over