18-12887486-T-C

Variant names:

• chr18-12887486-T-C
• rs12607710
• ENST00000592059.5:c.-228-28232A>G

Variant summary

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

The ENST00000592059.5(PTPN2):​c.-228-28232A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,154 control chromosomes in the GnomAD database, including 4,104 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 0.21 (4104 hom., cov: 32)
• Consequence: PTPN2 ENST00000592059.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854
• Publications: 8 publications found

Genes affected

PTPN2 (HGNC:9650): (protein tyrosine phosphatase non-receptor type 2) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000592059.5	c.-228-28232A>G		intron_variant	Intron 1 of 4	4		ENSP00000466206.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32348 AN: 152036 Hom.: 4110 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.213 AC: 32352 AN: 152154 Hom.: 4104 Cov.: 32 AF XY: 0.217 AC XY: 16140 AN XY: 74388

African (AFR) AF: 0.127 AC: 5259 AN: 41532

American (AMR) AF: 0.262 AC: 4006 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3468

East Asian (EAS) AF: 0.509 AC: 2630 AN: 5162

South Asian (SAS) AF: 0.496 AC: 2391 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1664 AN: 10596

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14698 AN: 67976

Other (OTH) AF: 0.227 AC: 479 AN: 2112

Alfa AF: 0.225 Hom.: 6723

Bravo AF: 0.214

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.69
PhyloP100		0.85

Splicing

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

Other links and lift over

dbSNP: rs12607710; hg19: chr18-12887485;