Genetic Variant HS6ST2:p.Gln626Gln (chrX-132628283-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001394073.1(HS6ST2):c.1878G>A(p.Gln626Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000313 in 1,054,273 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000031 ( 0 hom. 19 hem. )

Consequence

HS6ST2
NM_001394073.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.365

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 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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-132628283-C-T is Benign according to our data. Variant chrX-132628283-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 932641.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.365 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 19 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.1878G>A	p.Gln626Gln	synonymous	Exon 5 of 5	NP_001381002.1	Q96MM7-4
HS6ST2	NM_001077188.2		c.1878G>A	p.Gln626Gln	synonymous	Exon 6 of 6	NP_001070656.1	Q96MM7-4
HS6ST2	NM_001394074.1		c.1758G>A	p.Gln586Gln	synonymous	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.1878G>A	p.Gln626Gln	synonymous	Exon 5 of 5	ENSP00000359870.3	Q96MM7-4
HS6ST2	ENST00000406696.5	TSL:1	c.1440G>A	p.Gln480Gln	synonymous	Exon 5 of 5	ENSP00000384013.5	Q96MM7-3
HS6ST2	ENST00000521489.5	TSL:5	c.1878G>A	p.Gln626Gln	synonymous	Exon 6 of 6	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000686

AC:

AN:

116643

AF XY:

0.000121

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:

0.0000313

AC:

AN:

1054273

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

344961

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24916

American (AMR)

AF:

0.00

AC:

AN:

27937

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18635

East Asian (EAS)

AF:

0.00

AC:

AN:

27139

South Asian (SAS)

AF:

0.000581

AC:

AN:

49876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37699

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

819573

Other (OTH)

AF:

0.0000901

AC:

AN:

44414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.42

(source)

DANN

Benign

0.59

PhyloP100

0.36

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over