NM_012262.4:c.125-66195T>G

Variant names:

• chr1-87006739-T-G
• rs10747335
• NM_012262.4:c.125-66195T>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.125-66195T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,926 control chromosomes in the GnomAD database, including 39,122 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 0.70 (39122 hom., cov: 32)
• Consequence: HS2ST1 NM_012262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 3 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: AR, Unknown Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ENSG00000267561 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.945 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS2ST1	NM_012262.4	MANE Select	c.125-66195T>G		intron	N/A	NP_036394.1
	HS2ST1	NM_001134492.2		c.125-66195T>G		intron	N/A	NP_001127964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS2ST1	ENST00000370550.10	TSL:1 MANE Select	c.125-66195T>G		intron	N/A	ENSP00000359581.4
	ENSG00000267561	ENST00000370548.3	TSL:2	c.46+13612T>G		intron	N/A	ENSP00000359579.1
	HS2ST1	ENST00000370551.8	TSL:1	c.125-66195T>G		intron	N/A	ENSP00000359582.3

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105770 AN: 151808 Hom.: 39128 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.696 AC: 105802 AN: 151926 Hom.: 39122 Cov.: 32 AF XY: 0.704 AC XY: 52241 AN XY: 74234

African (AFR) AF: 0.426 AC: 17653 AN: 41450

American (AMR) AF: 0.807 AC: 12321 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2829 AN: 3468

East Asian (EAS) AF: 0.968 AC: 5015 AN: 5182

South Asian (SAS) AF: 0.821 AC: 3952 AN: 4812

European-Finnish (FIN) AF: 0.798 AC: 8427 AN: 10562

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53076 AN: 67862

Other (OTH) AF: 0.735 AC: 1552 AN: 2112

Alfa AF: 0.729 Hom.: 11395

Bravo AF: 0.688

Asia WGS AF: 0.819 AC: 2829 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.45
DANN	Benign	0.61
PhyloP100		-1.2
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: rs10747335; hg19: chr1-87472422; COSMIC: COSV63349164;