18-12877061-A-G

Variant names:

• chr18-12877061-A-G
• rs7234029
• NM_002828.4:c.69+7012T>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.69+7012T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,098 control chromosomes in the GnomAD database, including 7,339 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 0.26 (7339 hom., cov: 32)
• Consequence: PTPN2 NM_002828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 60 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN2	NM_002828.4	MANE Select	c.69+7012T>C		intron	N/A	NP_002819.2	P17706-1
	PTPN2	NM_001207013.2		c.69+7012T>C		intron	N/A	NP_001193942.1	P17706-4
	PTPN2	NM_080422.3		c.69+7012T>C		intron	N/A	NP_536347.1	P17706-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN2	ENST00000309660.10	TSL:1 MANE Select	c.69+7012T>C		intron	N/A	ENSP00000311857.3	P17706-1
	PTPN2	ENST00000591115.5	TSL:1	c.69+7012T>C		intron	N/A	ENSP00000466936.1	P17706-4
	PTPN2	ENST00000327283.7	TSL:1	c.69+7012T>C		intron	N/A	ENSP00000320298.3	P17706-2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40110 AN: 151980 Hom.: 7315 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.264 AC: 40181 AN: 152098 Hom.: 7339 Cov.: 32 AF XY: 0.263 AC XY: 19557 AN XY: 74368

African (AFR) AF: 0.521 AC: 21588 AN: 41432

American (AMR) AF: 0.168 AC: 2561 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1548 AN: 5178

South Asian (SAS) AF: 0.172 AC: 829 AN: 4826

European-Finnish (FIN) AF: 0.173 AC: 1836 AN: 10588

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10732 AN: 68000

Other (OTH) AF: 0.231 AC: 488 AN: 2114

Alfa AF: 0.224 Hom.: 2296

Bravo AF: 0.276

Asia WGS AF: 0.224 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.055
DANN	Benign	0.38
PhyloP100		-2.3
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: rs7234029; hg19: chr18-12877060;