20-47771969-T-C

Position:

• chr20-47771969-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULF2	NM_001387048.1	c.-101+13374A>G		intron_variant		ENST00000688720.1	NP_001373977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULF2	ENST00000688720.1	c.-101+13374A>G		intron_variant			NM_001387048.1	ENSP00000508753.1

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

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.536

Alfa AF: 0.516 Hom.: 26061

Bravo AF: 0.552

Asia WGS AF: 0.747 AC: 2594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.28
DANN	Benign	0.43

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: rs4810685; hg19: chr20-46400713;