rs514000

Variant names:

• chr18-12854073-C-T
• rs514000
• NM_002828.4:c.160+5091G>A

Variant summary

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

The NM_002828.4(PTPN2):​c.160+5091G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 151,982 control chromosomes in the GnomAD database, including 41,472 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 0.71 (41472 hom., cov: 31)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN2	NM_002828.4	MANE Select	c.160+5091G>A		intron	N/A	NP_002819.2
	PTPN2	NM_001207013.2		c.160+5091G>A		intron	N/A	NP_001193942.1
	PTPN2	NM_080422.3		c.160+5091G>A		intron	N/A	NP_536347.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN2	ENST00000309660.10	TSL:1 MANE Select	c.160+5091G>A		intron	N/A	ENSP00000311857.3
	PTPN2	ENST00000591115.5	TSL:1	c.160+5091G>A		intron	N/A	ENSP00000466936.1
	PTPN2	ENST00000327283.7	TSL:1	c.160+5091G>A		intron	N/A	ENSP00000320298.3

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108614 AN: 151862 Hom.: 41463 Cov.: 31

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.715 AC: 108653 AN: 151982 Hom.: 41472 Cov.: 31 AF XY: 0.716 AC XY: 53192 AN XY: 74282

African (AFR) AF: 0.422 AC: 17467 AN: 41412

American (AMR) AF: 0.819 AC: 12521 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3027 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3309 AN: 5146

South Asian (SAS) AF: 0.820 AC: 3956 AN: 4826

European-Finnish (FIN) AF: 0.823 AC: 8680 AN: 10548

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57056 AN: 67974

Other (OTH) AF: 0.750 AC: 1586 AN: 2114

Alfa AF: 0.757 Hom.: 5896

Bravo AF: 0.701

Asia WGS AF: 0.750 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.71
DANN	Benign	0.78
PhyloP100		-1.5
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: rs514000; hg19: chr18-12854072;