rs267606357

Variant names:

• chrX-132628506-C-A
• NM_001394073.1:c.1655G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-132628506-C-A
• chrX-132628506-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394073.1(HS6ST2):​c.1655G>T​(p.Arg552Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,963 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: HS6ST2 NM_001394073.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23837027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1	c.1655G>T	p.Arg552Leu	missense_variant	Exon 5 of 5	ENST00000370833.7	NP_001381002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS6ST2	ENST00000370833.7	c.1655G>T	p.Arg552Leu	missense_variant	Exon 5 of 5	5	NM_001394073.1	ENSP00000359870.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097963 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363433

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T;.;.;T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.87	.;.;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.14	N;.;.;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.52	N;N;.;.
REVEL	Benign	0.20
Sift	Benign	0.19	T;T;.;.
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.0010	B;.;.;B
Vest4		0.15
MutPred		0.51		Loss of methylation at K513 (P = 0.0448);.;.;Loss of methylation at K513 (P = 0.0448);
MVP		0.89
MPC		0.91
ClinPred		0.29	T
GERP RS		4.2
Varity_R		0.099
gMVP		0.67

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-131762534;