18-12857759-G-A

Variant names:

• chr18-12857759-G-A
• rs62097857
• NM_002828.4:c.160+1405C>T

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+1405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 152,120 control chromosomes in the GnomAD database, including 100 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 0.030 (100 hom., cov: 32)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 21 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0907 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+1405C>T		intron	N/A	NP_002819.2
	PTPN2	NM_001207013.2		c.160+1405C>T		intron	N/A	NP_001193942.1
	PTPN2	NM_080422.3		c.160+1405C>T		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+1405C>T		intron	N/A	ENSP00000311857.3
	PTPN2	ENST00000591115.5	TSL:1	c.160+1405C>T		intron	N/A	ENSP00000466936.1
	PTPN2	ENST00000327283.7	TSL:1	c.160+1405C>T		intron	N/A	ENSP00000320298.3

Frequencies

GnomAD3 genomes AF: 0.0299 AC: 4548 AN: 152002 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00771

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0985

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0263

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

GnomAD4 genome AF: 0.0299 AC: 4545 AN: 152120 Hom.: 100 Cov.: 32 AF XY: 0.0306 AC XY: 2274 AN XY: 74370

African (AFR) AF: 0.00769 AC: 319 AN: 41498

American (AMR) AF: 0.0205 AC: 313 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3470

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5178

South Asian (SAS) AF: 0.0980 AC: 471 AN: 4806

European-Finnish (FIN) AF: 0.0300 AC: 317 AN: 10584

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2827 AN: 67984

Other (OTH) AF: 0.0260 AC: 55 AN: 2116

Alfa AF: 0.0271 Hom.: 34

Bravo AF: 0.0257

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		0.051
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: rs62097857; hg19: chr18-12857758;