chr20-47658268-C-G

Position:

• chr20-47658268-C-G

Variant summary

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

The NM_001387048.1(SULF2):​c.*94G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 1,384,818 control chromosomes in the GnomAD database, including 557,361 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 0.92 (64981 hom., cov: 33)
  • Exomes 𝑓: 0.89 (492380 hom.)
• Consequence: SULF2 NM_001387048.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULF2	NM_001387048.1	c.*94G>C		3_prime_UTR_variant	21/21	ENST00000688720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULF2	ENST00000688720.1	c.*94G>C		3_prime_UTR_variant	21/21		NM_001387048.1	P3

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140434 AN: 152176 Hom.: 64922 Cov.: 33

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.930

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.930

GnomAD4 exome AF: 0.893 AC: 1101048 AN: 1232524 Hom.: 492380 Cov.: 17 AF XY: 0.894 AC XY: 558612 AN XY: 624684

Gnomad4 AFR exome AF: 0.981

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.936

Gnomad4 EAS exome AF: 0.974

Gnomad4 SAS exome AF: 0.913

Gnomad4 FIN exome AF: 0.907

Gnomad4 NFE exome AF: 0.882

Gnomad4 OTH exome AF: 0.903

GnomAD4 genome AF: 0.923 AC: 140551 AN: 152294 Hom.: 64981 Cov.: 33 AF XY: 0.927 AC XY: 69038 AN XY: 74448

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.928

Gnomad4 ASJ AF: 0.930

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.931

Alfa AF: 0.902 Hom.: 7737

Bravo AF: 0.928

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.41

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: rs444271; hg19: chr20-46287012;