NM_001394073.1:c.1878G>A

Variant names:

• chrX-132628283-C-T
• rs760879396
• NM_001394073.1:c.1878G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001394073.1(HS6ST2):​c.1878G>A​(p.Gln626Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000313 in 1,054,273 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000031 (0 hom. 19 hem.)
• Consequence: HS6ST2 NM_001394073.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Paganini-Miozzo syndrome

  Inheritance: Unknown, XL Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000296977 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-132628283-C-T is Benign according to our data. Variant chrX-132628283-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 932641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.365 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 19 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394073.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	NM_001394073.1	MANE Select	c.1878G>A	p.Gln626Gln	synonymous	Exon 5 of 5	NP_001381002.1	Q96MM7-4
	HS6ST2	NM_001077188.2		c.1878G>A	p.Gln626Gln	synonymous	Exon 6 of 6	NP_001070656.1	Q96MM7-4
	HS6ST2	NM_001394074.1		c.1758G>A	p.Gln586Gln	synonymous	Exon 3 of 3	NP_001381003.1	Q96MM7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS6ST2	ENST00000370833.7	TSL:5 MANE Select	c.1878G>A	p.Gln626Gln	synonymous	Exon 5 of 5	ENSP00000359870.3	Q96MM7-4
	HS6ST2	ENST00000406696.5	TSL:1	c.1440G>A	p.Gln480Gln	synonymous	Exon 5 of 5	ENSP00000384013.5	Q96MM7-3
	HS6ST2	ENST00000521489.5	TSL:5	c.1878G>A	p.Gln626Gln	synonymous	Exon 6 of 6	ENSP00000429473.1	Q96MM7-4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000686 AC: 8 AN: 116643 AF XY: 0.000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000313 AC: 33 AN: 1054273 Hom.: 0 Cov.: 30 AF XY: 0.0000551 AC XY: 19 AN XY: 344961

African (AFR) AF: 0.00 AC: 0 AN: 24916

American (AMR) AF: 0.00 AC: 0 AN: 27937

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18635

East Asian (EAS) AF: 0.00 AC: 0 AN: 27139

South Asian (SAS) AF: 0.000581 AC: 29 AN: 49876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37699

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 819573

Other (OTH) AF: 0.0000901 AC: 4 AN: 44414

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.42
DANN	Benign	0.59
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs760879396; hg19: chrX-131762311;