18-12821594-A-G

Variant names:

• chr18-12821594-A-G
• rs2847281
• NM_002828.4:c.495+4216T>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.495+4216T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,170 control chromosomes in the GnomAD database, including 8,935 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 0.32 (8935 hom., cov: 33)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 41 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.495+4216T>C		intron_variant	Intron 5 of 8	ENST00000309660.10	NP_002819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660.10	c.495+4216T>C		intron_variant	Intron 5 of 8	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48074 AN: 152052 Hom.: 8927 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.316 AC: 48104 AN: 152170 Hom.: 8935 Cov.: 33 AF XY: 0.317 AC XY: 23576 AN XY: 74394

African (AFR) AF: 0.132 AC: 5505 AN: 41550

American (AMR) AF: 0.414 AC: 6323 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3472

East Asian (EAS) AF: 0.141 AC: 731 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4824

European-Finnish (FIN) AF: 0.449 AC: 4746 AN: 10578

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27090 AN: 67972

Other (OTH) AF: 0.343 AC: 725 AN: 2112

Alfa AF: 0.372 Hom.: 43679

Bravo AF: 0.310

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.81
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2847281; hg19: chr18-12821593;