chr20-47663405-T-G

Variant names:

• chr20-47663405-T-G
• rs2235734
• NM_001387048.1:c.2227+48A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387052.1(SULF2):​c.2230+48A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,599,120 control chromosomes in the GnomAD database, including 95,898 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8448 hom., cov: 32)
  • Exomes 𝑓: 0.35 (87450 hom.)
• Consequence: SULF2 NM_001387052.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387052.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF2	NM_001387048.1	MANE Select	c.2227+48A>C		intron	N/A	NP_001373977.1
	SULF2	NM_001387052.1		c.2230+48A>C		intron	N/A	NP_001373981.1
	SULF2	NM_001387053.1		c.2230+48A>C		intron	N/A	NP_001373982.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF2	ENST00000688720.1	MANE Select	c.2227+48A>C		intron	N/A	ENSP00000508753.1
	SULF2	ENST00000359930.8	TSL:1	c.2227+48A>C		intron	N/A	ENSP00000353007.4
	SULF2	ENST00000484875.5	TSL:1	c.2227+48A>C		intron	N/A	ENSP00000418290.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49882 AN: 151946 Hom.: 8454 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.353

GnomAD2 exomes AF: 0.337 AC: 81432 AN: 241600 AF XY: 0.342

Gnomad AFR exome AF: 0.297

Gnomad AMR exome AF: 0.390

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.252

Gnomad FIN exome AF: 0.209

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.345 AC: 499309 AN: 1447056 Hom.: 87450 Cov.: 33 AF XY: 0.346 AC XY: 248921 AN XY: 719968

African (AFR) AF: 0.306 AC: 10192 AN: 33262

American (AMR) AF: 0.387 AC: 17093 AN: 44138

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 10030 AN: 25930

East Asian (EAS) AF: 0.286 AC: 11355 AN: 39638

South Asian (SAS) AF: 0.362 AC: 31150 AN: 85944

European-Finnish (FIN) AF: 0.211 AC: 9271 AN: 43970

Middle Eastern (MID) AF: 0.472 AC: 2186 AN: 4636

European-Non Finnish (NFE) AF: 0.349 AC: 387324 AN: 1109576

Other (OTH) AF: 0.345 AC: 20708 AN: 59962

GnomAD4 genome AF: 0.328 AC: 49882 AN: 152064 Hom.: 8448 Cov.: 32 AF XY: 0.323 AC XY: 23998 AN XY: 74338

African (AFR) AF: 0.297 AC: 12339 AN: 41480

American (AMR) AF: 0.398 AC: 6090 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3466

East Asian (EAS) AF: 0.259 AC: 1334 AN: 5160

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4822

European-Finnish (FIN) AF: 0.199 AC: 2110 AN: 10588

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23541 AN: 67942

Other (OTH) AF: 0.356 AC: 751 AN: 2112

Alfa AF: 0.347 Hom.: 21679

Bravo AF: 0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.66
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2235734; hg19: chr20-46292149;