chr18-12843138-T-C

Position:

• chr18-12843138-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002828.4(PTPN2):​c.161-6247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,026 control chromosomes in the GnomAD database, including 2,275 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 0.17 (2275 hom., cov: 31)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPN2	NM_002828.4	c.161-6247A>G		intron_variant		ENST00000309660.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPN2	ENST00000309660.10	c.161-6247A>G		intron_variant		1	NM_002828.4	A1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25624 AN: 151908 Hom.: 2268 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.169 AC: 25658 AN: 152026 Hom.: 2275 Cov.: 31 AF XY: 0.171 AC XY: 12676 AN XY: 74288

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.161

Alfa AF: 0.154 Hom.: 1877

Bravo AF: 0.168

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs11875687; hg19: chr18-12843137;