18-12809341-A-G

Variant names:

• chr18-12809341-A-G
• rs1893217
• NM_002828.4:c.858+4862T>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.858+4862T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,242 control chromosomes in the GnomAD database, including 1,411 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 0.12 (1411 hom., cov: 32)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 226 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=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 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.858+4862T>C		intron	N/A	NP_002819.2
	PTPN2	NM_001207013.2		c.927+4862T>C		intron	N/A	NP_001193942.1
	PTPN2	NM_080422.3		c.858+4862T>C		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.858+4862T>C		intron	N/A	ENSP00000311857.3
	PTPN2	ENST00000591115.5	TSL:1	c.927+4862T>C		intron	N/A	ENSP00000466936.1
	PTPN2	ENST00000327283.7	TSL:1	c.858+4862T>C		intron	N/A	ENSP00000320298.3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18947 AN: 152124 Hom.: 1410 Cov.: 32

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.124 AC: 18946 AN: 152242 Hom.: 1411 Cov.: 32 AF XY: 0.126 AC XY: 9389 AN XY: 74432

African (AFR) AF: 0.0579 AC: 2405 AN: 41560

American (AMR) AF: 0.0965 AC: 1477 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 336 AN: 3466

East Asian (EAS) AF: 0.172 AC: 889 AN: 5168

South Asian (SAS) AF: 0.189 AC: 911 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1595 AN: 10596

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11014 AN: 68014

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.148 Hom.: 8454

Bravo AF: 0.116

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.86
PhyloP100		-0.65
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: rs1893217; hg19: chr18-12809340;