X-132628318-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001394073.1(HS6ST2):c.1843C>T(p.Arg615Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,165,869 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R615Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000027 ( 0 hom. 8 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.368

Publications

2 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 Gene-Disease associations (from GenCC):

Paganini-Miozzo syndrome
Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

HS6ST2 links:

ENSG00000296977 (HGNC:):

ENSG00000296977 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07105851).

BS2

High Hemizygotes in GnomAdExome4 at 8 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.1843C>T	p.Arg615Trp	missense	Exon 5 of 5	NP_001381002.1	Q96MM7-4
HS6ST2	NM_001077188.2		c.1843C>T	p.Arg615Trp	missense	Exon 6 of 6	NP_001070656.1	Q96MM7-4
HS6ST2	NM_001394074.1		c.1723C>T	p.Arg575Trp	missense	Exon 3 of 3	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.1843C>T	p.Arg615Trp	missense	Exon 5 of 5	ENSP00000359870.3	Q96MM7-4
HS6ST2	ENST00000406696.5	TSL:1	c.1405C>T	p.Arg469Trp	missense	Exon 5 of 5	ENSP00000384013.5	Q96MM7-3
HS6ST2	ENST00000521489.5	TSL:5	c.1843C>T	p.Arg615Trp	missense	Exon 6 of 6	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

110967

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000566

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000171

AC:

AN:

117280

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000149

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:

0.0000218

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000265

AC:

AN:

1054902

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

344946

show subpopulations

African (AFR)

AF:

0.0000401

AC:

AN:

24944

American (AMR)

AF:

0.00

AC:

AN:

27999

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18650

East Asian (EAS)

AF:

0.00

AC:

AN:

27183

South Asian (SAS)

AF:

0.00

AC:

AN:

50104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37773

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4082

European-Non Finnish (NFE)

AF:

0.0000317

AC:

AN:

819718

Other (OTH)

AF:

0.0000225

AC:

AN:

44449

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

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:

0.0000270

AC:

AN:

110967

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33213

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30449

American (AMR)

AF:

0.00

AC:

AN:

10414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3545

South Asian (SAS)

AF:

0.00

AC:

AN:

2582

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000566

AC:

AN:

53024

Other (OTH)

AF:

0.00

AC:

AN:

1483

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000102

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000317

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000232

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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.047

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.67

M_CAP

Benign

0.065

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.81

PhyloP100

0.37

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.96

REVEL

Benign

0.13

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.030

Polyphen

0.0

Vest4

0.087

MVP

0.76

MPC

0.89

ClinPred

0.065

GERP RS

2.4

Varity_R

0.094

gMVP

0.51

Mutation Taster

=85/15

polymorphism

(source)

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

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