rs77573141

Variant names:

• chr18-12817161-C-A
• NM_002828.4:c.700G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-12817161-C-A
• chr18-12817161-C-G
• chr18-12817161-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002828.4(PTPN2):​c.700G>T​(p.Val234Phe) variant causes a missense 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 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3530724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.700G>T	p.Val234Phe	missense_variant	Exon 6 of 9	ENST00000309660.10	NP_002819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660.10	c.700G>T	p.Val234Phe	missense_variant	Exon 6 of 9	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	.;.;.;D;.;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.84	T;T;T;T;T;.;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.35	T;T;T;T;T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	2.0	M;.;M;M;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.0	D;.;D;D;.;.;.
REVEL	Uncertain	0.54
Sift	Uncertain	0.0080	D;.;D;D;.;.;.
Sift4G	Pathogenic	0.0010	D;D;D;D;D;.;.
Polyphen		0.066	B;.;.;B;.;.;.
Vest4		0.59
MutPred		0.47		Loss of ubiquitination at K238 (P = 0.1079);.;Loss of ubiquitination at K238 (P = 0.1079);Loss of ubiquitination at K238 (P = 0.1079);.;.;.;
MVP		0.94
MPC		0.14
ClinPred		0.95	D
GERP RS		2.3
Varity_R		0.38
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-12817160;