chrX-132628920-G-A

Variant names:

• chrX-132628920-G-A
• NM_001394073.1:c.1241C>T

Variant summary

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

The NM_001394073.1(HS6ST2):​c.1241C>T​(p.Pro414Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,886 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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: 0.0000018 (0 hom. 1 hem.)
• Consequence: HS6ST2 NM_001394073.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.81

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 rank	MANE	Protein	UniProt
HS6ST2	NM_001394073.1	c.1241C>T	p.Pro414Leu	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.1241C>T	p.Pro414Leu	missense_variant	Exon 5 of 5	5	NM_001394073.1	ENSP00000359870.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097886 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363370

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: 0.00000238

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	0.13
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;.;T;.
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	.;.;T;T;T
M_CAP	Pathogenic	0.40	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.69	N;.;.;N;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.6	N;N;.;.;.
REVEL	Uncertain	0.30
Sift	Benign	0.031	D;D;.;.;.
Sift4G	Uncertain	0.033	D;D;D;D;.
Polyphen		0.0030	B;.;.;B;.
Vest4		0.35
MutPred		0.52		Loss of loop (P = 0.0203);.;.;Loss of loop (P = 0.0203);.;
MVP		0.83
MPC		0.63
ClinPred		0.76	D
GERP RS		3.2
Varity_R		0.18
gMVP		0.76

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-131762948; COSMIC: COSV63710527;