chrX-132669169-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001394073.1(HS6ST2):​c.1011C>T​(p.Asn337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000729 in 1,207,049 control chromosomes in the GnomAD database, including 1 homozygotes. There are 42 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 2 hem., cov: 22)
Exomes 𝑓: 0.000074 ( 1 hom. 40 hem. )

Consequence

HS6ST2
NM_001394073.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.989
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-AS1 (HGNC:40870): (HS6ST2 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant X-132669169-G-A is Benign according to our data. Variant chrX-132669169-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661454.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.989 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HS6ST2NM_001394073.1 linkuse as main transcriptc.1011C>T p.Asn337= synonymous_variant 4/5 ENST00000370833.7 NP_001381002.1
HS6ST2-AS1NR_046691.1 linkuse as main transcriptn.225-394G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HS6ST2ENST00000370833.7 linkuse as main transcriptc.1011C>T p.Asn337= synonymous_variant 4/55 NM_001394073.1 ENSP00000359870 Q96MM7-4
HS6ST2-AS1ENST00000455269.1 linkuse as main transcriptn.225-394G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000630
AC:
7
AN:
111085
Hom.:
0
Cov.:
22
AF XY:
0.0000600
AC XY:
2
AN XY:
33323
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:
0.00118
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000566
Gnomad OTH
AF:
0.000669
GnomAD3 exomes
AF:
0.000135
AC:
24
AN:
177636
Hom.:
0
AF XY:
0.000230
AC XY:
15
AN XY:
65096
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000370
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000864
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000739
AC:
81
AN:
1095964
Hom.:
1
Cov.:
28
AF XY:
0.000111
AC XY:
40
AN XY:
361532
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000285
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000178
Gnomad4 OTH exome
AF:
0.0000435
GnomAD4 genome
AF:
0.0000630
AC:
7
AN:
111085
Hom.:
0
Cov.:
22
AF XY:
0.0000600
AC XY:
2
AN XY:
33323
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00118
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000566
Gnomad4 OTH
AF:
0.000669
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2022HS6ST2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
CADD
Benign
1.4
DANN
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
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.

Other links and lift over

dbSNP: rs369708094; hg19: chrX-131803197; COSMIC: COSV100897158; API