16-22830171-T-G

Variant names:

• chr16-22830171-T-G
• rs2283524
• NM_006043.2:c.485+15076T>G

Variant summary

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

The NM_006043.2(HS3ST2):​c.485+15076T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 150,388 control chromosomes in the GnomAD database, including 1,325 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 0.13 (1325 hom., cov: 32)
• Consequence: HS3ST2 NM_006043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 10 publications found

Genes affected

HS3ST2 (HGNC:5195): (heparan sulfate-glucosamine 3-sulfotransferase 2) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It is a type II integral membrane protein and possesses heparan sulfate glucosaminyl 3-O-sulfotransferase activity. This gene is expressed predominantly in brain and may play a role in the nervous system. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HS3ST2	NM_006043.2	c.485+15076T>G		intron_variant	Intron 1 of 1	ENST00000261374.4	NP_006034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HS3ST2	ENST00000261374.4	c.485+15076T>G		intron_variant	Intron 1 of 1	1	NM_006043.2	ENSP00000261374.3
HS3ST2	ENST00000473392.1	n.486-3105T>G		intron_variant	Intron 1 of 3	5		ENSP00000454505.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19263 AN: 150268 Hom.: 1318 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.0284

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.128 AC: 19298 AN: 150388 Hom.: 1325 Cov.: 32 AF XY: 0.131 AC XY: 9605 AN XY: 73502

African (AFR) AF: 0.0921 AC: 3813 AN: 41386

American (AMR) AF: 0.105 AC: 1599 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3442

East Asian (EAS) AF: 0.129 AC: 665 AN: 5168

South Asian (SAS) AF: 0.223 AC: 1052 AN: 4724

European-Finnish (FIN) AF: 0.154 AC: 1609 AN: 10440

Middle Eastern (MID) AF: 0.198 AC: 57 AN: 288

European-Non Finnish (NFE) AF: 0.147 AC: 9834 AN: 66752

Other (OTH) AF: 0.130 AC: 272 AN: 2098

Alfa AF: 0.140 Hom.: 6812

Bravo AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2283524; hg19: chr16-22841492;