rs16939895

Variant names:

• chr18-12821904-G-A
• rs16939895
• NM_002828.4:c.495+3906C>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.495+3906C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,116 control chromosomes in the GnomAD database, including 2,405 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 0.17 (2405 hom., cov: 32)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 19 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.495+3906C>T		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+3906C>T		intron_variant	Intron 5 of 8	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26269 AN: 151998 Hom.: 2401 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.173 AC: 26297 AN: 152116 Hom.: 2405 Cov.: 32 AF XY: 0.175 AC XY: 13027 AN XY: 74376

African (AFR) AF: 0.187 AC: 7740 AN: 41470

American (AMR) AF: 0.142 AC: 2173 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 441 AN: 3468

East Asian (EAS) AF: 0.357 AC: 1847 AN: 5172

South Asian (SAS) AF: 0.181 AC: 874 AN: 4826

European-Finnish (FIN) AF: 0.177 AC: 1878 AN: 10584

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10842 AN: 67996

Other (OTH) AF: 0.168 AC: 355 AN: 2116

Alfa AF: 0.160 Hom.: 347

Bravo AF: 0.172

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.23
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: rs16939895; hg19: chr18-12821903;