Genetic Variant HS6ST2:p.Lys353Arg (chrX-132669122-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001394073.1(HS6ST2):c.1058A>G(p.Lys353Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000776 in 1,199,174 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 54 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000084 ( 0 hom. 54 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.07

Publications

0 publications found

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:

HS6ST2-AS1 (HGNC:40870): (HS6ST2 antisense RNA 1)

HS6ST2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03985825).

BS2

High Hemizygotes in GnomAdExome4 at 54 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394073.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS6ST2	NM_001394073.1	MANE Select	c.1058A>G	p.Lys353Arg	missense	Exon 4 of 5	NP_001381002.1	Q96MM7-4
HS6ST2	NM_001077188.2		c.1058A>G	p.Lys353Arg	missense	Exon 5 of 6	NP_001070656.1	Q96MM7-4
HS6ST2	NM_001394074.1		c.948-40029A>G		intron	N/A	NP_001381003.1	Q96MM7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HS6ST2	ENST00000370833.7	TSL:5 MANE Select	c.1058A>G	p.Lys353Arg	missense	Exon 4 of 5	ENSP00000359870.3	Q96MM7-4
HS6ST2	ENST00000406696.5	TSL:1	c.620A>G	p.Lys207Arg	missense	Exon 4 of 5	ENSP00000384013.5	Q96MM7-3
HS6ST2	ENST00000521489.5	TSL:5	c.1058A>G	p.Lys353Arg	missense	Exon 5 of 6	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111824

Hom.:

Cov.:

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:

0.000766

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000130

AC:

AN:

176793

AF XY:

0.000264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000837

AC:

AN:

1087299

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

AN XY:

353611

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26176

American (AMR)

AF:

0.00

AC:

AN:

35124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19295

East Asian (EAS)

AF:

0.00

AC:

AN:

30090

South Asian (SAS)

AF:

0.00155

AC:

AN:

53594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40485

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4106

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

832678

Other (OTH)

AF:

0.000175

AC:

AN:

45751

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000179

AC:

AN:

111875

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34025

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30787

American (AMR)

AF:

0.00

AC:

AN:

10549

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.00

AC:

AN:

3571

South Asian (SAS)

AF:

0.000769

AC:

AN:

2602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53159

Other (OTH)

AF:

0.00

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000174

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.61

PhyloP100

3.1

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.25

REVEL

Benign

0.26

Sift

Benign

0.13

Sift4G

Benign

0.35

Vest4

0.22

MVP

0.63

MPC

0.57

ClinPred

0.58

GERP RS

4.1

gMVP

0.65

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over