2-219296777-C-G

Position:

• chr2-219296777-C-G

Variant summary

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

The NM_002846.4(PTPRN):​c.2282G>C​(p.Arg761Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PTPRN NM_002846.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

Genes affected

PTPRN (HGNC:9676): (protein tyrosine phosphatase receptor type N) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single catalytic domain, and thus represents a receptor-type PTP. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Dec 2010]

PTPRN (HGNC:):

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/exons	MANE	Protein	UniProt
PTPRN	NM_002846.4	c.2282G>C	p.Arg761Pro	missense_variant	16/23	ENST00000295718.7	NP_002837.1
PTPRN	NM_001199763.2	c.2195G>C	p.Arg732Pro	missense_variant	15/22		NP_001186692.1
PTPRN	NM_001199764.2	c.2012G>C	p.Arg671Pro	missense_variant	16/23		NP_001186693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRN	ENST00000295718.7	c.2282G>C	p.Arg761Pro	missense_variant	16/23	1	NM_002846.4	ENSP00000295718.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.2282G>C (p.R761P) alteration is located in exon 16 (coding exon 16) of the PTPRN gene. This alteration results from a G to C substitution at nucleotide position 2282, causing the arginine (R) at amino acid position 761 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	.;D;.
Eigen	Benign	0.022
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	.;N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.8	D;D;.
REVEL	Benign	0.11
Sift	Benign	0.033	D;D;.
Sift4G	Benign	0.092	T;T;T
Polyphen		0.69	.;P;.
Vest4		0.57
MutPred		0.41		.;Gain of glycosylation at R761 (P = 0.0252);.;
MVP		0.38
MPC		1.5
ClinPred		0.95	D
GERP RS		3.4
Varity_R		0.93
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-220161499;