Variant 20-47664171-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001387048.1(SULF2):c.2016A>T(p.Lys672Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,460,678 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000041 ( 2 hom. )

Consequence

SULF2
NM_001387048.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.403

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06358576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULF2	NM_001387048.1 linkuse as main transcript	c.2016A>T	p.Lys672Asn	missense_variant	15/21	ENST00000688720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULF2	ENST00000688720.1 linkuse as main transcript	c.2016A>T	p.Lys672Asn	missense_variant	15/21		NM_001387048.1	P3	Q8IWU5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000603

AC:

AN:

248580

Hom.:

AF XY:

0.0000891

AC XY:

AN XY:

134656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000497

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000411

AC:

AN:

1460678

Hom.:

Cov.:

AF XY:

0.0000647

AC XY:

AN XY:

726474

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000675

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.2016A>T (p.K672N) alteration is located in exon 15 (coding exon 14) of the SULF2 gene. This alteration results from a A to T substitution at nucleotide position 2016, causing the lysine (K) at amino acid position 672 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.095

T;T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.86

M_CAP

Benign

0.014

MetaRNN

Benign

0.064

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

0.75

N;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.10

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.45

MutPred

0.20

Loss of methylation at K672 (P = 0.0112);Loss of methylation at K672 (P = 0.0112);Loss of methylation at K672 (P = 0.0112);

MVP

0.068

MPC

0.45

ClinPred

0.059

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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