20-47663405-T-G

Position:

• chr20-47663405-T-G

Variant summary

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

The NM_001387048.1(SULF2):​c.2227+48A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,599,120 control chromosomes in the GnomAD database, including 95,898 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 0.33 (8448 hom., cov: 32)
  • Exomes 𝑓: 0.35 (87450 hom.)
• Consequence: SULF2 NM_001387048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULF2	NM_001387048.1	c.2227+48A>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.2227+48A>C		intron_variant			NM_001387048.1	ENSP00000508753	P3

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49882 AN: 151946 Hom.: 8454 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.353

GnomAD3 exomes AF: 0.337 AC: 81432 AN: 241600 Hom.: 14277 AF XY: 0.342 AC XY: 44817 AN XY: 131204

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.252

Gnomad SAS exome AF: 0.359

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.345 AC: 499309 AN: 1447056 Hom.: 87450 Cov.: 33 AF XY: 0.346 AC XY: 248921 AN XY: 719968

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.349

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.328 AC: 49882 AN: 152064 Hom.: 8448 Cov.: 32 AF XY: 0.323 AC XY: 23998 AN XY: 74338

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.356

Alfa AF: 0.348 Hom.: 13976

Bravo AF: 0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.66

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: rs2235734; hg19: chr20-46292149;