20-47771969-T-C

Variant names:

• chr20-47771969-T-C
• rs4810685
• NM_001387048.1:c.-101+13374A>G

Variant summary

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

The NM_001387048.1(SULF2):​c.-101+13374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,010 control chromosomes in the GnomAD database, including 23,583 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 0.55 (23583 hom., cov: 32)
• Consequence: SULF2 NM_001387048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 11 publications found

Genes affected

SULF2 (HGNC:20392): (sulfatase 2) Heparan sulfate proteoglycans (HSPGs) act as coreceptors for numerous heparin-binding growth factors and cytokines and are involved in cell signaling. Heparan sulfate 6-O-endosulfatases, such as SULF2, selectively remove 6-O-sulfate groups from heparan sulfate. This activity modulates the effects of heparan sulfate by altering binding sites for signaling molecules (Dai et al., 2005 [PubMed 16192265]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387048.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF2	NM_001387048.1	MANE Select	c.-101+13374A>G		intron	N/A	NP_001373977.1	Q8IWU5-1
	SULF2	NM_001387052.1		c.-101+14079A>G		intron	N/A	NP_001373981.1
	SULF2	NM_001387053.1		c.-101+13866A>G		intron	N/A	NP_001373982.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF2	ENST00000688720.1	MANE Select	c.-101+13374A>G		intron	N/A	ENSP00000508753.1	Q8IWU5-1
	SULF2	ENST00000359930.8	TSL:1	c.-101+13866A>G		intron	N/A	ENSP00000353007.4	Q8IWU5-1
	SULF2	ENST00000484875.5	TSL:1	c.-101+14079A>G		intron	N/A	ENSP00000418290.1	Q8IWU5-1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83186 AN: 151892 Hom.: 23565 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.548 AC: 83239 AN: 152010 Hom.: 23583 Cov.: 32 AF XY: 0.549 AC XY: 40764 AN XY: 74278

African (AFR) AF: 0.662 AC: 27448 AN: 41436

American (AMR) AF: 0.449 AC: 6868 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1901 AN: 3468

East Asian (EAS) AF: 0.868 AC: 4489 AN: 5172

South Asian (SAS) AF: 0.635 AC: 3063 AN: 4820

European-Finnish (FIN) AF: 0.448 AC: 4736 AN: 10566

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32956 AN: 67948

Other (OTH) AF: 0.536 AC: 1130 AN: 2110

Alfa AF: 0.516 Hom.: 61148

Bravo AF: 0.552

Asia WGS AF: 0.747 AC: 2594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.43
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: rs4810685; hg19: chr20-46400713;