dbSNP rs17452535: HS2ST1:c.125-49964A>G (chr1-87022970-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.394

Publications

4 publications found

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 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)

HS2ST1 links:

ENSG00000267561 (HGNC:):

ENSG00000267561 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS2ST1	NM_012262.4 link	c.125-49964A>G		intron_variant	Intron 1 of 6	ENST00000370550.10	NP_036394.1	Q7LGA3-1
HS2ST1	NM_001134492.2 link	c.125-49964A>G		intron_variant	Intron 1 of 4		NP_001127964.1	Q7LGA3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS2ST1	ENST00000370550.10 link	c.125-49964A>G		intron_variant	Intron 1 of 6	1	NM_012262.4	ENSP00000359581.4		Q7LGA3-1
ENSG00000267561	ENST00000370548.3 link	c.46+29843A>G		intron_variant	Intron 1 of 7	2		ENSP00000359579.1

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20711

AN:

152056

Hom.:

1493

Cov.:

show subpopulations

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.:

AF XY:

0.134

AC XY:

9959

AN XY:

74396

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9342

AN:

67986

Other (OTH)

AF:

0.124

AC:

262

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

907

1814

2720

3627

4534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.73

(source)

DANN

Benign

0.54

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over