1-87084175-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012262.4(HS2ST1):c.364-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 1,441,548 control chromosomes in the GnomAD database, including 632,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (65015 hom., cov: 31)
  • Exomes 𝑓: 0.94 (567074 hom.)
• Consequence: HS2ST1 NM_012262.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-87084175-A-G is Benign according to our data. Variant chr1-87084175-A-G is described in ClinVar as [Benign]. Clinvar id is 2585672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HS2ST1	NM_012262.4	c.364-19A>G		intron_variant		ENST00000370550.10
HS2ST1	NM_001134492.2	c.364-19A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HS2ST1	ENST00000370550.10	c.364-19A>G		intron_variant		1	NM_012262.4	P1

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140458 AN: 152090 Hom.: 64966 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.929

GnomAD3 exomes AF: 0.941 AC: 207790 AN: 220756 Hom.: 97915 AF XY: 0.941 AC XY: 112738 AN XY: 119746

Gnomad AFR exome AF: 0.875

Gnomad AMR exome AF: 0.969

Gnomad ASJ exome AF: 0.911

Gnomad EAS exome AF: 0.996

Gnomad SAS exome AF: 0.951

Gnomad FIN exome AF: 0.950

Gnomad NFE exome AF: 0.935

Gnomad OTH exome AF: 0.936

GnomAD4 exome AF: 0.938 AC: 1208892 AN: 1289340 Hom.: 567074 Cov.: 17 AF XY: 0.938 AC XY: 607355 AN XY: 647756

Gnomad4 AFR exome AF: 0.883

Gnomad4 AMR exome AF: 0.966

Gnomad4 ASJ exome AF: 0.908

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.950

Gnomad4 FIN exome AF: 0.950

Gnomad4 NFE exome AF: 0.936

Gnomad4 OTH exome AF: 0.933

GnomAD4 genome AF: 0.924 AC: 140565 AN: 152208 Hom.: 65015 Cov.: 31 AF XY: 0.927 AC XY: 68957 AN XY: 74408

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.929

Alfa AF: 0.919 Hom.: 13094

Bravo AF: 0.924

Asia WGS AF: 0.962 AC: 3339 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurofacioskeletal syndrome with or without renal agenesis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.2
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2798675; hg19: chr1-87549858;