chr2-130356160-G-A

Position:

chr2-130356160-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014369.4(PTPN18):c.53G>A(p.Arg18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,312,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R18L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

PTPN18
NM_014369.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.195

Variant links:

Genes affected

PTPN18 (HGNC:9649): (protein tyrosine phosphatase non-receptor type 18) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, the mitotic cycle, and oncogenic transformation. This PTP contains a PEST motif, which often serves as a protein-protein interaction domain, and may be related to protein intracellular half-live. This protein can differentially dephosphorylate autophosphorylated tyrosine kinases that are overexpressed in tumor tissues, and it appears to regulate HER2, a member of the epidermal growth factor receptor family of receptor tyrosine kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

PTPN18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.075774044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PTPN18	NM_014369.4 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/15	ENST00000175756.10
PTPN18	NM_001142370.2 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/11
PTPN18	XM_006712417.2 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/16
PTPN18	XM_006712416.5 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN18	ENST00000175756.10 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/15	1	NM_014369.4	P1	Q99952-1
PTPN18	ENST00000347849.7 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant	1/11	1			Q99952-2
PTPN18	ENST00000489215.5 linkuse as main transcript	n.106G>A		non_coding_transcript_exon_variant	1/4	4
PTPN18	ENST00000428843.5 linkuse as main transcript	c.53G>A	p.Arg18Gln	missense_variant, NMD_transcript_variant	1/9	3

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000681

AC:

AN:

1160648

Hom.:

Cov.:

AF XY:

0.0000858

AC XY:

AN XY:

559122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000859

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000877

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151920

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.000137

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.53G>A (p.R18Q) alteration is located in exon 1 (coding exon 1) of the PTPN18 gene. This alteration results from a G to A substitution at nucleotide position 53, causing the arginine (R) at amino acid position 18 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0090

T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.17

N;N

REVEL

Benign

0.038

Sift

Benign

0.20

T;D

Sift4G

Benign

0.32

T;T

Polyphen

0.99

D;.

Vest4

0.081

MVP

0.22

MPC

0.21

ClinPred

0.28

GERP RS

-0.73

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.2

Varity_R

0.12

gMVP

0.11

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over