2-219290270-C-A

Variant names:

• chr2-219290270-C-A
• rs139964061
• NM_002846.4:c.2896G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002846.4(PTPRN):​c.2896G>T​(p.Val966Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 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. V966M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRN NM_002846.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.25
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
PTPRN	NM_002846.4	c.2896G>T	p.Val966Leu	missense_variant	Exon 23 of 23	ENST00000295718.7	NP_002837.1
PTPRN	NM_001199763.2	c.2809G>T	p.Val937Leu	missense_variant	Exon 22 of 22		NP_001186692.1
PTPRN	NM_001199764.2	c.2626G>T	p.Val876Leu	missense_variant	Exon 23 of 23		NP_001186693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN	ENST00000295718.7	c.2896G>T	p.Val966Leu	missense_variant	Exon 23 of 23	1	NM_002846.4	ENSP00000295718.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	.;D;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Uncertain	0.017	D
MutationAssessor	Benign	0.57	.;N;.
PhyloP100		7.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.9	D;D;.
REVEL	Pathogenic	0.78
Sift	Uncertain	0.023	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.97	.;D;.
Vest4		0.63
MutPred		0.67		.;Loss of stability (P = 0.5583);.;
MVP		0.86
MPC		1.3
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.91
gMVP		0.88
Mutation Taster		=35/65	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs139964061; hg19: chr2-220154992;