Variant 20-47661855-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001387048.1(SULF2):c.2412C>A(p.Asn804Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SULF2
NM_001387048.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.221

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULF2	NM_001387048.1 linkuse as main transcript	c.2412C>A	p.Asn804Lys	missense_variant	18/21	ENST00000688720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULF2	ENST00000688720.1 linkuse as main transcript	c.2412C>A	p.Asn804Lys	missense_variant	18/21		NM_001387048.1	P3	Q8IWU5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442260

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716320

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.10e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 15, 2022

The c.2412C>A (p.N804K) alteration is located in exon 18 (coding exon 17) of the SULF2 gene. This alteration results from a C to A substitution at nucleotide position 2412, causing the asparagine (N) at amino acid position 804 to be replaced by a lysine (K). 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

Pathogenic

0.72

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

D;D;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.70

LIST_S2

Pathogenic

1.0

.;D;D

M_CAP

Benign

0.066

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.6

M;M;M

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.22

Sift

Benign

0.042

D;D;D

Sift4G

Benign

0.15

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.83

MutPred

0.38

Gain of ubiquitination at N804 (P = 0.0325);Gain of ubiquitination at N804 (P = 0.0325);Gain of ubiquitination at N804 (P = 0.0325);

MVP

0.16

MPC

1.2

ClinPred

0.99

GERP RS

-4.1

Varity_R

0.45

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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