Variant 20-47666256-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001387048.1(SULF2):c.1805+4A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 150,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SULF2
NM_001387048.1 splice_donor_region, intron

Scores

Splicing: ADA: 0.9759

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.25

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 Benign. Variant got -16 ACMG points.

BP6

Variant 20-47666256-T-C is Benign according to our data. Variant chr20-47666256-T-C is described in ClinVar as [Benign]. Clinvar id is 769999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULF2	NM_001387048.1 linkuse as main transcript	c.1805+4A>G		splice_donor_region_variant, intron_variant		ENST00000688720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULF2	ENST00000688720.1 linkuse as main transcript	c.1805+4A>G		splice_donor_region_variant, intron_variant			NM_001387048.1	P3	Q8IWU5-1

Frequencies

GnomAD3 genomes

AF:

0.00999

AC:

1501

AN:

150210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0725

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.0573

Gnomad SAS

AF:

0.00376

Gnomad FIN

AF:

0.00648

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00828

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00241

AC:

3477

AN:

1442700

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1715

AN XY:

718822

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0361

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0504

Gnomad4 SAS exome

AF:

0.000841

Gnomad4 FIN exome

AF:

0.00351

Gnomad4 NFE exome

AF:

0.0000810

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.0100

AC:

1505

AN:

150332

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

819

AN XY:

73380

show subpopulations

Gnomad4 AFR

AF:

0.00124

Gnomad4 AMR

AF:

0.0728

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.0570

Gnomad4 SAS

AF:

0.00377

Gnomad4 FIN

AF:

0.00648

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00819

Alfa

AF:

0.00353

Hom.:

EpiCase

AF:

0.000327

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Benign

0.68

SpliceAI score (max)

0.56

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.56

Position offset: 4

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