rs768757935

Variant names:

• chr7-157578098-G-C
• NM_002847.5:c.2539C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-157578098-G-C
• chr7-157578098-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002847.5(PTPRN2):​c.2539C>G​(p.Pro847Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P847T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTPRN2 NM_002847.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55

Genes affected

PTPRN2 (HGNC:9677): (protein tyrosine phosphatase receptor type N2) This gene encodes a protein with sequence similarity to receptor-like protein tyrosine phosphatases. However, tyrosine phosphatase activity has not been experimentally validated for this protein. Studies of the rat ortholog suggest that the encoded protein may instead function as a phosphatidylinositol phosphatase with the ability to dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 4,5-diphosphate, and this function may be involved in the regulation of insulin secretion. This protein has been identified as an autoantigen in insulin-dependent diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.2539C>G	p.Pro847Ala	missense_variant	Exon 18 of 23	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.2539C>G	p.Pro847Ala	missense_variant	Exon 18 of 23	1	NM_002847.5	ENSP00000374069.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;.;.;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.56	.;.;.;N;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.9	D;D;D;D;.
REVEL	Benign	0.25
Sift	Benign	0.097	T;T;T;T;.
Sift4G	Benign	0.32	T;T;T;T;.
Polyphen		0.11	B;B;.;B;.
Vest4		0.58
MutPred		0.46		.;.;.;Gain of sheet (P = 0.1539);.;
MVP		0.55
MPC		0.68
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.44
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-157370790;