20-47661506-T-C

Position:

• chr20-47661506-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.2494+267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 298,968 control chromosomes in the GnomAD database, including 10,444 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 0.25 (5058 hom., cov: 31)
  • Exomes 𝑓: 0.26 (5386 hom.)
• Consequence: SULF2 NM_001387048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.794

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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULF2	NM_001387048.1	c.2494+267A>G		intron_variant		ENST00000688720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULF2	ENST00000688720.1	c.2494+267A>G		intron_variant			NM_001387048.1	P3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38414 AN: 151970 Hom.: 5058 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.263 AC: 38588 AN: 146880 Hom.: 5386 Cov.: 3 AF XY: 0.264 AC XY: 19438 AN XY: 73612

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.253 AC: 38424 AN: 152088 Hom.: 5058 Cov.: 31 AF XY: 0.247 AC XY: 18353 AN XY: 74368

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.276

Alfa AF: 0.294 Hom.: 7742

Bravo AF: 0.255

Asia WGS AF: 0.234 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.9
DANN	Benign	0.80

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: rs2281279; hg19: chr20-46290250; COSMIC: COSV59069425; COSMIC: COSV59069425;