20-47666256-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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, single submitter B:1
• Conservation: PhyloP100: 3.25

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]

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 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	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	c.1805+4A>G		splice_donor_region_variant, intron_variant			NM_001387048.1	P3

Frequencies

GnomAD3 genomes AF: 0.00999 AC: 1501 AN: 150210 Hom.: 0 Cov.: 32

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.: 0 Cov.: 34 AF XY: 0.00239 AC XY: 1715 AN XY: 718822

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.: 0 Cov.: 32 AF XY: 0.0112 AC XY: 819 AN XY: 73380

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.: 0

EpiCase AF: 0.000327

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	20
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

Other links and lift over

dbSNP: rs73624692; hg19: chr20-46295000; COSMIC: COSV63416562; COSMIC: COSV63416562;