Variant 1-87084186-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012262.4(HS2ST1):c.364-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,554,762 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 10 hom., cov: 32)

Exomes 𝑓: 0.011 ( 106 hom. )

Consequence

HS2ST1
NM_012262.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004880

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.268

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-87084186-C-T is Benign according to our data. Variant chr1-87084186-C-T is described in ClinVar as [Benign]. Clinvar id is 707157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS2ST1	NM_012262.4 linkuse as main transcript	c.364-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370550.10
HS2ST1	NM_001134492.2 linkuse as main transcript	c.364-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS2ST1	ENST00000370550.10 linkuse as main transcript	c.364-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012262.4	P1	Q7LGA3-1

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

1268

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00924

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00374

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00908

AC:

2111

AN:

232562

Hom.:

AF XY:

0.00927

AC XY:

1165

AN XY:

125698

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00595

Gnomad ASJ exome

AF:

0.00871

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00428

Gnomad FIN exome

AF:

0.00480

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0110

AC:

15366

AN:

1402544

Hom.:

106

Cov.:

AF XY:

0.0108

AC XY:

7579

AN XY:

699144

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00729

Gnomad4 ASJ exome

AF:

0.00818

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00416

Gnomad4 FIN exome

AF:

0.00569

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00920

GnomAD4 genome

AF:

0.00832

AC:

1267

AN:

152218

Hom.:

Cov.:

AF XY:

0.00758

AC XY:

564

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00923

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.00537

Gnomad4 NFE

AF:

0.0135

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00873

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Neurofacioskeletal syndrome with or without renal agenesis

Benign:2

Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 18, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	HS2ST1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Sep 21, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.3

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.0060

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over