rs478582

Variant names:

• chr18-12835977-T-C
• rs478582
• NM_002828.4:c.261+814A>G

Variant summary

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

The NM_002828.4(PTPN2):​c.261+814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,106 control chromosomes in the GnomAD database, including 11,110 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 0.35 (11110 hom., cov: 31)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 49 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 (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.261+814A>G		intron_variant	Intron 3 of 8	ENST00000309660.10	NP_002819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660.10	c.261+814A>G		intron_variant	Intron 3 of 8	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53335 AN: 151988 Hom.: 11101 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.351 AC: 53366 AN: 152106 Hom.: 11110 Cov.: 31 AF XY: 0.351 AC XY: 26110 AN XY: 74360

African (AFR) AF: 0.140 AC: 5829 AN: 41514

American (AMR) AF: 0.447 AC: 6833 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1769 AN: 3466

East Asian (EAS) AF: 0.143 AC: 740 AN: 5180

South Asian (SAS) AF: 0.252 AC: 1216 AN: 4822

European-Finnish (FIN) AF: 0.498 AC: 5272 AN: 10576

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30344 AN: 67966

Other (OTH) AF: 0.391 AC: 825 AN: 2108

Alfa AF: 0.434 Hom.: 22333

Bravo AF: 0.343

Asia WGS AF: 0.244 AC: 846 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	2.5
DANN	Benign	0.33
PhyloP100		-0.12
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: rs478582; hg19: chr18-12835976;