rs2300290

Variant names:

• chr12-15582508-G-A
• rs2300290
• NM_030667.3:c.3255+707G>A

Variant summary

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

The NM_030667.3(PTPRO):​c.3255+707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,164 control chromosomes in the GnomAD database, including 2,798 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 0.19 (2798 hom., cov: 33)
• Consequence: PTPRO NM_030667.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 11 publications found

Genes affected

PTPRO (HGNC:9678): (protein tyrosine phosphatase receptor type O) This gene encodes a member of the R3 subtype family of receptor-type protein tyrosine phosphatases. These proteins are localized to the apical surface of polarized cells and may have tissue-specific functions through activation of Src family kinases. This gene contains two distinct promoters, and alternatively spliced transcript variants encoding multiple isoforms have been observed. The encoded proteins may have multiple isoform-specific and tissue-specific functions, including the regulation of osteoclast production and activity, inhibition of cell proliferation and facilitation of apoptosis. This gene is a candidate tumor suppressor, and decreased expression of this gene has been observed in several types of cancer. [provided by RefSeq, May 2011]

PTPRO Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 6

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030667.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	NM_030667.3	MANE Select	c.3255+707G>A		intron	N/A	NP_109592.1	Q16827-1
	PTPRO	NM_002848.4		c.3171+707G>A		intron	N/A	NP_002839.1	Q16827-2
	PTPRO	NM_030669.3		c.822+707G>A		intron	N/A	NP_109594.1	Q16827-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRO	ENST00000281171.9	TSL:1 MANE Select	c.3255+707G>A		intron	N/A	ENSP00000281171.4	Q16827-1
	PTPRO	ENST00000348962.7	TSL:1	c.3171+707G>A		intron	N/A	ENSP00000343434.2	Q16827-2
	PTPRO	ENST00000442921.7	TSL:1	c.822+707G>A		intron	N/A	ENSP00000404188.2	Q16827-3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28216 AN: 152046 Hom.: 2801 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.222

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.186 AC: 28229 AN: 152164 Hom.: 2798 Cov.: 33 AF XY: 0.187 AC XY: 13927 AN XY: 74400

African (AFR) AF: 0.138 AC: 5709 AN: 41514

American (AMR) AF: 0.204 AC: 3109 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3466

East Asian (EAS) AF: 0.259 AC: 1341 AN: 5186

South Asian (SAS) AF: 0.189 AC: 912 AN: 4828

European-Finnish (FIN) AF: 0.203 AC: 2147 AN: 10578

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13302 AN: 68006

Other (OTH) AF: 0.219 AC: 463 AN: 2110

Alfa AF: 0.198 Hom.: 13229

Bravo AF: 0.185

Asia WGS AF: 0.202 AC: 700 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.63
PhyloP100		-0.17
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: rs2300290; hg19: chr12-15735442;