rs2847297

Variant names:

• chr18-12797695-A-G
• rs2847297
• NM_002828.4:c.1041-3210T>C

Variant summary

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

The NM_002828.4(PTPN2):​c.1041-3210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,920 control chromosomes in the GnomAD database, including 12,653 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 0.39 (12653 hom., cov: 31)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 54 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.1041-3210T>C		intron_variant	Intron 8 of 8	ENST00000309660.10	NP_002819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660.10	c.1041-3210T>C		intron_variant	Intron 8 of 8	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59517 AN: 151802 Hom.: 12637 Cov.: 31

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.392 AC: 59584 AN: 151920 Hom.: 12653 Cov.: 31 AF XY: 0.389 AC XY: 28877 AN XY: 74256

African (AFR) AF: 0.566 AC: 23446 AN: 41402

American (AMR) AF: 0.288 AC: 4403 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3466

East Asian (EAS) AF: 0.317 AC: 1638 AN: 5168

South Asian (SAS) AF: 0.281 AC: 1354 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3680 AN: 10534

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23233 AN: 67956

Other (OTH) AF: 0.352 AC: 743 AN: 2108

Alfa AF: 0.350 Hom.: 44348

Bravo AF: 0.396

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.59
PhyloP100		-0.28
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: rs2847297; hg19: chr18-12797694;