rs45450798

Positions:

• chr18-12792941-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002828.4(PTPN2):​c.*1337G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 984,206 control chromosomes in the GnomAD database, including 13,156 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 0.12 (1413 hom., cov: 32)
  • Exomes 𝑓: 0.17 (11743 hom.)
• Consequence: PTPN2 NM_002828.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.*1337G>C		3_prime_UTR_variant	9/9	ENST00000309660.10	NP_002819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660	c.*1337G>C		3_prime_UTR_variant	9/9	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18943 AN: 152068 Hom.: 1412 Cov.: 32

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.0970

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.166 AC: 137839 AN: 832020 Hom.: 11743 Cov.: 29 AF XY: 0.166 AC XY: 63739 AN XY: 384274

Gnomad4 AFR exome AF: 0.0520

Gnomad4 AMR exome AF: 0.0772

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.124 AC: 18942 AN: 152186 Hom.: 1413 Cov.: 32 AF XY: 0.126 AC XY: 9387 AN XY: 74394

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.0985

Gnomad4 ASJ AF: 0.0970

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.117

Alfa AF: 0.137 Hom.: 192

Bravo AF: 0.116

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs45450798; hg19: chr18-12792940;