7-157595259-GGC-CGT

Variant names:

• chr7-157595259-GGC-CGT
• NM_002847.5:c.2473_2475delGCCinsACG
• PTPRN2 p.Ala825Thr

Variant summary

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

The NM_002847.5(PTPRN2):​c.2473_2475delGCCinsACG​(p.Ala825Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A825V) 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: 7.51
• Publications: 0 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]

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.2473_2475delGCCinsACG	p.Ala825Thr	missense	N/A	NP_002838.2	Q92932-1
	PTPRN2	NM_001308268.2		c.2542_2544delGCCinsACG	p.Ala848Thr	missense	N/A	NP_001295197.1	Q92932-3
	PTPRN2	NM_130842.4		c.2422_2424delGCCinsACG	p.Ala808Thr	missense	N/A	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.2473_2475delGCCinsACG	p.Ala825Thr	missense	N/A	ENSP00000374069.4	Q92932-1
	PTPRN2	ENST00000389416.8	TSL:1	c.2422_2424delGCCinsACG	p.Ala808Thr	missense	N/A	ENSP00000374067.4	Q92932-4
	PTPRN2	ENST00000389413.7	TSL:1	c.2386_2388delGCCinsACG	p.Ala796Thr	missense	N/A	ENSP00000374064.3	Q92932-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-157387951;