chr18-12792941-C-G

Variant names:

• chr18-12792941-C-G
• rs45450798
• NM_002828.4:c.*1337G>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.*1337G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 984,206 control chromosomes in the GnomAD database, including 13,156 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 0.12 (1413 hom., cov: 32)
  • Exomes 𝑓: 0.17 (11743 hom.)
• Consequence: PTPN2 NM_002828.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 33 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN2	NM_002828.4	c.*1337G>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000309660.10	NP_002819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660.10	c.*1337G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_002828.4	ENSP00000311857.3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18943 AN: 152068 Hom.: 1412 Cov.: 32

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0986

Gnomad ASJ AF: 0.0970

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.166 AC: 137839 AN: 832020 Hom.: 11743 Cov.: 29 AF XY: 0.166 AC XY: 63739 AN XY: 384274

African (AFR) AF: 0.0520 AC: 819 AN: 15758

American (AMR) AF: 0.0772 AC: 76 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 545 AN: 5144

East Asian (EAS) AF: 0.184 AC: 667 AN: 3628

South Asian (SAS) AF: 0.193 AC: 3174 AN: 16432

European-Finnish (FIN) AF: 0.116 AC: 32 AN: 276

Middle Eastern (MID) AF: 0.117 AC: 190 AN: 1618

European-Non Finnish (NFE) AF: 0.168 AC: 127748 AN: 760914

Other (OTH) AF: 0.168 AC: 4588 AN: 27266

GnomAD4 genome AF: 0.124 AC: 18942 AN: 152186 Hom.: 1413 Cov.: 32 AF XY: 0.126 AC XY: 9387 AN XY: 74394

African (AFR) AF: 0.0575 AC: 2388 AN: 41546

American (AMR) AF: 0.0985 AC: 1506 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0970 AC: 336 AN: 3464

East Asian (EAS) AF: 0.170 AC: 882 AN: 5180

South Asian (SAS) AF: 0.188 AC: 908 AN: 4820

European-Finnish (FIN) AF: 0.151 AC: 1595 AN: 10572

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11005 AN: 67998

Other (OTH) AF: 0.117 AC: 246 AN: 2110

Alfa AF: 0.137 Hom.: 192

Bravo AF: 0.116

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		-0.38
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: rs45450798; hg19: chr18-12792940;