18-12809341-A-C

Variant names:

• chr18-12809341-A-C
• rs1893217
• NM_002828.4:c.858+4862T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002828.4(PTPN2):​c.858+4862T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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>G		intron	N/A	NP_002819.2
	PTPN2	NM_001207013.2		c.927+4862T>G		intron	N/A	NP_001193942.1
	PTPN2	NM_080422.3		c.858+4862T>G		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>G		intron	N/A	ENSP00000311857.3
	PTPN2	ENST00000591115.5	TSL:1	c.927+4862T>G		intron	N/A	ENSP00000466936.1
	PTPN2	ENST00000327283.7	TSL:1	c.858+4862T>G		intron	N/A	ENSP00000320298.3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.93
DANN	Benign	0.86
PhyloP100		-0.65

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;