chrX-132628521-T-A

Variant names:

• chrX-132628521-T-A
• NM_001394073.1:c.1640A>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001394073.1(HS6ST2):​c.1640A>T​(p.His547Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,097,999 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000017 (0 hom. 2 hem.)
• Consequence: HS6ST2 NM_001394073.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1	c.1640A>T	p.His547Leu	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.1640A>T	p.His547Leu	missense_variant	Exon 5 of 5	5	NM_001394073.1	ENSP00000359870.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000173 AC: 19 AN: 1097999 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2 AN XY: 363465

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: 0.0000226

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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T;.;.;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	.;.;T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.97	L;.;.;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.0	D;D;.;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.013	D;D;.;.
Sift4G	Uncertain	0.044	D;D;D;D
Polyphen		0.96	P;.;.;P
Vest4		0.52
MutPred		0.60		Gain of stability (P = 0.0538);.;.;Gain of stability (P = 0.0538);
MVP		0.89
MPC		1.8
ClinPred		0.95	D
GERP RS		6.0
Varity_R		0.65
gMVP		0.74

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-131762549;