rs193920806

Variant names:

• chr7-157621367-A-G
• rs193920806
• NM_002847.5:c.2339T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002847.5(PTPRN2):​c.2339T>C​(p.Leu780Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,611,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 39)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: PTPRN2 NM_002847.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 8.52
• Publications: 1 publications found

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]

ENSG00000222012 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002847.5. 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
	PTPRN2	NM_002847.5	MANE Select	c.2339T>C	p.Leu780Pro	missense	Exon 15 of 23	NP_002838.2	Q92932-1
	PTPRN2	NM_001308268.2		c.2408T>C	p.Leu803Pro	missense	Exon 15 of 23	NP_001295197.1	Q92932-3
	PTPRN2	NM_130842.4		c.2288T>C	p.Leu763Pro	missense	Exon 14 of 22	NP_570857.2	Q92932-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRN2	ENST00000389418.9	TSL:1 MANE Select	c.2339T>C	p.Leu780Pro	missense	Exon 15 of 23	ENSP00000374069.4	Q92932-1
	PTPRN2	ENST00000389416.8	TSL:1	c.2288T>C	p.Leu763Pro	missense	Exon 14 of 22	ENSP00000374067.4	Q92932-4
	PTPRN2	ENST00000389413.7	TSL:1	c.2252T>C	p.Leu751Pro	missense	Exon 14 of 22	ENSP00000374064.3	Q92932-2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152256 Hom.: 0 Cov.: 39

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 250748 AF XY: 0.000111

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000511

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 244 AN: 1459644 Hom.: 0 Cov.: 39 AF XY: 0.000138 AC XY: 100 AN XY: 726114

African (AFR) AF: 0.0000897 AC: 3 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86188

European-Finnish (FIN) AF: 0.000320 AC: 17 AN: 53134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000195 AC: 217 AN: 1110442

Other (OTH) AF: 0.000116 AC: 7 AN: 60300

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152256 Hom.: 0 Cov.: 39 AF XY: 0.0000941 AC XY: 7 AN XY: 74384

African (AFR) AF: 0.0000965 AC: 4 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000111 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	0.0090	T
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		8.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.82
MVP		0.59
MPC		0.99
ClinPred		0.65	D
GERP RS		5.0
PromoterAI		-0.0068	Neutral
Varity_R		0.89
gMVP		0.85
Mutation Taster		=33/67	disease causing

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: rs193920806; hg19: chr7-157414059; COSMIC: COSV67037443; COSMIC: COSV67037443;