rs2281279

Variant names:

• chr20-47661506-T-C
• rs2281279
• NM_001387048.1:c.2494+267A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SULF2	NM_001387048.1	c.2494+267A>G		intron_variant	Intron 18 of 20	ENST00000688720.1	NP_001373977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULF2	ENST00000688720.1	c.2494+267A>G		intron_variant	Intron 18 of 20		NM_001387048.1	ENSP00000508753.1

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

African (AFR) AF: 0.202 AC: 933 AN: 4626

American (AMR) AF: 0.225 AC: 889 AN: 3956

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1689 AN: 5258

East Asian (EAS) AF: 0.162 AC: 1865 AN: 11534

South Asian (SAS) AF: 0.261 AC: 494 AN: 1890

European-Finnish (FIN) AF: 0.199 AC: 4898 AN: 24552

Middle Eastern (MID) AF: 0.363 AC: 264 AN: 728

European-Non Finnish (NFE) AF: 0.293 AC: 24966 AN: 85126

Other (OTH) AF: 0.281 AC: 2590 AN: 9210

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

African (AFR) AF: 0.197 AC: 8161 AN: 41478

American (AMR) AF: 0.248 AC: 3786 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3472

East Asian (EAS) AF: 0.180 AC: 930 AN: 5178

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4820

European-Finnish (FIN) AF: 0.189 AC: 1999 AN: 10588

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20090 AN: 67958

Other (OTH) AF: 0.276 AC: 582 AN: 2112

Alfa AF: 0.288 Hom.: 11429

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
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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