chrX-132669186-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001394073.1(HS6ST2):​c.994G>T​(p.Gly332Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,093,781 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

HS6ST2
NM_001394073.1 missense

Scores

1
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34072173).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HS6ST2NM_001394073.1 linkuse as main transcriptc.994G>T p.Gly332Cys missense_variant 4/5 ENST00000370833.7 NP_001381002.1
HS6ST2-AS1NR_046691.1 linkuse as main transcriptn.225-377C>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.994G>T p.Gly332Cys missense_variant 4/55 NM_001394073.1 ENSP00000359870 Q96MM7-4
HS6ST2-AS1ENST00000455269.1 linkuse as main transcriptn.225-377C>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
9.14e-7
AC:
1
AN:
1093781
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
359395
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000187
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 27, 2022The c.994G>T (p.G332C) alteration is located in exon 5 (coding exon 4) of the HS6ST2 gene. This alteration results from a G to T substitution at nucleotide position 994, causing the glycine (G) at amino acid position 332 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
21
DANN
Uncertain
1.0
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.50
.;T;T
M_CAP
Pathogenic
0.54
D
MetaRNN
Benign
0.34
T;T;T
MetaSVM
Benign
-0.60
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.020
N;.;.
REVEL
Benign
0.18
Sift
Uncertain
0.0030
D;.;.
Sift4G
Uncertain
0.023
D;D;.
Vest4
0.56
MVP
0.71
MPC
1.5
ClinPred
0.96
D
GERP RS
3.4
gMVP
0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-131803214; API