rs8083786

Variant names:

• chr18-12881362-A-G
• rs8083786
• NM_002828.4:c.69+2711T>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.69+2711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,064 control chromosomes in the GnomAD database, including 7,386 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 0.26 (7386 hom., cov: 32)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 22 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.69+2711T>C		intron_variant	Intron 1 of 8	ENST00000309660.10	NP_002819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660.10	c.69+2711T>C		intron_variant	Intron 1 of 8	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40178 AN: 151946 Hom.: 7356 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.265 AC: 40255 AN: 152064 Hom.: 7386 Cov.: 32 AF XY: 0.264 AC XY: 19586 AN XY: 74322

African (AFR) AF: 0.523 AC: 21662 AN: 41422

American (AMR) AF: 0.168 AC: 2568 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1547 AN: 5178

South Asian (SAS) AF: 0.171 AC: 823 AN: 4816

European-Finnish (FIN) AF: 0.173 AC: 1833 AN: 10574

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10735 AN: 67982

Other (OTH) AF: 0.232 AC: 489 AN: 2110

Alfa AF: 0.231 Hom.: 704

Bravo AF: 0.276

Asia WGS AF: 0.224 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.15
PhyloP100		-1.0
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: rs8083786; hg19: chr18-12881361;