Variant 20-47663617-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001387048.1(SULF2):c.2063G>A(p.Gly688Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000318 in 1,586,936 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 4 hom. )

Consequence

SULF2
NM_001387048.1 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008715332).

BP6

Variant 20-47663617-C-T is Benign according to our data. Variant chr20-47663617-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 770670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULF2	NM_001387048.1 linkuse as main transcript	c.2063G>A	p.Gly688Asp	missense_variant	16/21	ENST00000688720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULF2	ENST00000688720.1 linkuse as main transcript	c.2063G>A	p.Gly688Asp	missense_variant	16/21		NM_001387048.1	P3	Q8IWU5-1

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000607

AC:

139

AN:

228922

Hom.:

AF XY:

0.000751

AC XY:

AN XY:

122440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000459

Gnomad ASJ exome

AF:

0.000125

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00343

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000296

Gnomad OTH exome

AF:

0.000719

GnomAD4 exome

AF:

0.000320

AC:

459

AN:

1434616

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

297

AN XY:

710384

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000488

Gnomad4 ASJ exome

AF:

0.0000821

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00319

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.000507

GnomAD4 genome

AF:

0.000302

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000593

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;T;.

Eigen

Benign

-0.022

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0087

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.035

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.63

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.49

MVP

0.068

MPC

0.50

ClinPred

0.023

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over