chrX-132628542-T-C

Position:

• chrX-132628542-T-C

Variant summary

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

The NM_001394073.1(HS6ST2):​c.1619A>G​(p.Gln540Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,913 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: HS6ST2 NM_001394073.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS6ST2	NM_001394073.1	c.1619A>G	p.Gln540Arg	missense_variant	5/5	ENST00000370833.7	NP_001381002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS6ST2	ENST00000370833.7	c.1619A>G	p.Gln540Arg	missense_variant	5/5	5	NM_001394073.1	ENSP00000359870

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097913 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363379

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000356

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

HS6ST2: PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.65	.;.;T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.59	D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.0	L;.;.;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N;N;.;.
REVEL	Uncertain	0.56
Sift	Benign	0.089	T;T;.;.
Sift4G	Benign	0.10	T;T;T;T
Polyphen		0.92	P;.;.;P
Vest4		0.58
MutPred		0.49		Gain of MoRF binding (P = 0.0124);.;.;Gain of MoRF binding (P = 0.0124);
MVP		0.84
MPC		0.70
ClinPred		0.74	D
GERP RS		6.0
Varity_R		0.60
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-131762570;