dbSNP rs2281279: SULF2:c.2494+267A>G (chr20-47661506-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.794

Publications

18 publications found

Variant links:

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]

SULF2 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387048.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SULF2	NM_001387048.1	MANE Select	c.2494+267A>G	intron	N/A	NP_001373977.1	Q8IWU5-1
SULF2	NM_001387052.1		c.2497+267A>G	intron	N/A	NP_001373981.1
SULF2	NM_001387053.1		c.2497+267A>G	intron	N/A	NP_001373982.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SULF2	ENST00000688720.1	MANE Select	c.2494+267A>G	intron	N/A	ENSP00000508753.1	Q8IWU5-1
SULF2	ENST00000359930.8	TSL:1	c.2494+267A>G	intron	N/A	ENSP00000353007.4	Q8IWU5-1
SULF2	ENST00000484875.5	TSL:1	c.2494+267A>G	intron	N/A	ENSP00000418290.1	Q8IWU5-1

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38414

AN:

151970

Hom.:

5058

Cov.:

show subpopulations

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.:

AF XY:

0.264

AC XY:

19438

AN XY:

73612

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1364

2729

4093

5458

6822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.253

AC:

38424

AN:

152088

Hom.:

5058

Cov.:

AF XY:

0.247

AC XY:

18353

AN XY:

74368

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1472

2944

4416

5888

7360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.9

(source)

DANN

Benign

0.80

PhyloP100

0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over