20-47726848-A-G

Position:

• chr20-47726848-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387048.1(SULF2):​c.415+9855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,766 control chromosomes in the GnomAD database, including 5,371 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 0.26 (5371 hom., cov: 31)
• Consequence: SULF2 NM_001387048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULF2	NM_001387048.1	c.415+9855T>C		intron_variant		ENST00000688720.1	NP_001373977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULF2	ENST00000688720.1	c.415+9855T>C		intron_variant			NM_001387048.1	ENSP00000508753	P3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39809 AN: 151648 Hom.: 5362 Cov.: 31

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.263 AC: 39853 AN: 151766 Hom.: 5371 Cov.: 31 AF XY: 0.266 AC XY: 19723 AN XY: 74136

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.223

Alfa AF: 0.263 Hom.: 9996

Bravo AF: 0.252

Asia WGS AF: 0.297 AC: 1033 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	0.045
DANN	Benign	0.22

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: rs4810671; hg19: chr20-46355592;