rs17452535

Variant names:

• chr1-87022970-A-G
• rs17452535
• NM_012262.4:c.125-49964A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012262.4(HS2ST1):​c.125-49964A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,174 control chromosomes in the GnomAD database, including 1,497 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1497 hom., cov: 32)
• Consequence: HS2ST1 NM_012262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 4 publications found

Genes affected

HS2ST1 (HGNC:5193): (heparan sulfate 2-O-sulfotransferase 1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. This gene encodes a member of the heparan sulfate biosynthetic enzyme family that transfers sulfate to the 2 position of the iduronic acid residue of heparan sulfate. The disruption of this gene resulted in no kidney formation in knockout embryonic mice, indicating that the absence of this enzyme may interfere with the signaling required for kidney formation. Two alternatively spliced transcript variants that encode different proteins have been found for this gene. [provided by RefSeq, Aug 2008]

HS2ST1 Gene-Disease associations (from GenCC):

• neurofacioskeletal syndrome with or without renal agenesis

  Inheritance: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ENSG00000267561 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012262.4. 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
	HS2ST1	NM_012262.4	MANE Select	c.125-49964A>G		intron	N/A	NP_036394.1	Q7LGA3-1
	HS2ST1	NM_001134492.2		c.125-49964A>G		intron	N/A	NP_001127964.1	Q7LGA3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS2ST1	ENST00000370550.10	TSL:1 MANE Select	c.125-49964A>G		intron	N/A	ENSP00000359581.4	Q7LGA3-1
	ENSG00000267561	ENST00000370548.3	TSL:2	c.46+29843A>G		intron	N/A	ENSP00000359579.1
	HS2ST1	ENST00000370551.8	TSL:1	c.125-49964A>G		intron	N/A	ENSP00000359582.3	Q7LGA3-3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20711 AN: 152056 Hom.: 1493 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0762

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0999

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.123

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20741 AN: 152174 Hom.: 1497 Cov.: 32 AF XY: 0.134 AC XY: 9959 AN XY: 74396

African (AFR) AF: 0.178 AC: 7387 AN: 41504

American (AMR) AF: 0.102 AC: 1557 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0762 AC: 264 AN: 3464

East Asian (EAS) AF: 0.0262 AC: 136 AN: 5188

South Asian (SAS) AF: 0.123 AC: 593 AN: 4826

European-Finnish (FIN) AF: 0.0999 AC: 1059 AN: 10600

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9342 AN: 67986

Other (OTH) AF: 0.124 AC: 262 AN: 2112

Alfa AF: 0.137 Hom.: 968

Bravo AF: 0.138

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.73
DANN	Benign	0.54
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs17452535; hg19: chr1-87488653;