Genetic Variant HS6ST2:p.Gly355Glu (chrX-132669116-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001394073.1(HS6ST2):c.1064G>A(p.Gly355Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000672 in 1,189,643 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000056 ( 0 hom. 1 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2024608).

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.1064G>A	p.Gly355Glu	missense	Exon 4 of 5	NP_001381002.1	Q96MM7-4
HS6ST2	NM_001077188.2		c.1064G>A	p.Gly355Glu	missense	Exon 5 of 6	NP_001070656.1	Q96MM7-4
HS6ST2	NM_001394074.1		c.948-40023G>A		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.1064G>A	p.Gly355Glu	missense	Exon 4 of 5	ENSP00000359870.3	Q96MM7-4
HS6ST2	ENST00000406696.5	TSL:1	c.626G>A	p.Gly209Glu	missense	Exon 4 of 5	ENSP00000384013.5	Q96MM7-3
HS6ST2	ENST00000521489.5	TSL:5	c.1064G>A	p.Gly355Glu	missense	Exon 5 of 6	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000652

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000574

AC:

AN:

174137

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000820

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:

0.00000557

AC:

AN:

1078007

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

345787

show subpopulations

African (AFR)

AF:

0.000154

AC:

AN:

25972

American (AMR)

AF:

0.00

AC:

AN:

34906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19200

East Asian (EAS)

AF:

0.00

AC:

AN:

29988

South Asian (SAS)

AF:

0.00

AC:

AN:

52882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40445

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4087

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

825092

Other (OTH)

AF:

0.0000220

AC:

AN:

45435

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111636

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33836

show subpopulations

African (AFR)

AF:

0.0000651

AC:

AN:

30722

American (AMR)

AF:

0.00

AC:

AN:

10528

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3556

South Asian (SAS)

AF:

0.00

AC:

AN:

2578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6067

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53116

Other (OTH)

AF:

0.00

AC:

AN:

1520

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000827

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

0.17

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.38

M_CAP

Benign

0.038

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.79

PhyloP100

3.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.26

REVEL

Benign

0.17

Sift

Benign

0.24

Sift4G

Benign

0.19

Vest4

0.69

MVP

0.59

MPC

0.80

ClinPred

0.51

GERP RS

4.1

gMVP

0.74

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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