7-157540717-C-A

Variant names:

• chr7-157540717-C-A
• rs61757813
• NM_002847.5:c.3045G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_002847.5(PTPRN2):​c.3045G>T​(p.Gln1015His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00955 in 1,561,220 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1015R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0064 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0099 (86 hom.)
• Consequence: PTPRN2 NM_002847.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.61
• Publications: 9 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.114).
• BP6: Variant 7-157540717-C-A is Benign according to our data. Variant chr7-157540717-C-A is described in ClinVar as Benign. ClinVar VariationId is 774459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.3045G>T	p.Gln1015His	missense	Exon 23 of 23	NP_002838.2	Q92932-1
	PTPRN2	NM_001308268.2		c.3114G>T	p.Gln1038His	missense	Exon 23 of 23	NP_001295197.1	Q92932-3
	PTPRN2	NM_130842.4		c.2994G>T	p.Gln998His	missense	Exon 22 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.3045G>T	p.Gln1015His	missense	Exon 23 of 23	ENSP00000374069.4	Q92932-1
	PTPRN2	ENST00000389416.8	TSL:1	c.2994G>T	p.Gln998His	missense	Exon 22 of 22	ENSP00000374067.4	Q92932-4
	PTPRN2	ENST00000389413.7	TSL:1	c.2958G>T	p.Gln986His	missense	Exon 22 of 22	ENSP00000374064.3	Q92932-2

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 979 AN: 152208 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00604 AC: 1041 AN: 172386 AF XY: 0.00657

Gnomad AFR exome AF: 0.00162

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.0100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00261

Gnomad NFE exome AF: 0.0101

Gnomad OTH exome AF: 0.00699

GnomAD4 exome AF: 0.00989 AC: 13935 AN: 1408894 Hom.: 86 Cov.: 31 AF XY: 0.00977 AC XY: 6801 AN XY: 696236

African (AFR) AF: 0.00168 AC: 54 AN: 32102

American (AMR) AF: 0.00402 AC: 150 AN: 37326

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 260 AN: 25258

East Asian (EAS) AF: 0.0000818 AC: 3 AN: 36672

South Asian (SAS) AF: 0.00197 AC: 157 AN: 79756

European-Finnish (FIN) AF: 0.00243 AC: 121 AN: 49836

Middle Eastern (MID) AF: 0.00211 AC: 12 AN: 5700

European-Non Finnish (NFE) AF: 0.0118 AC: 12735 AN: 1083778

Other (OTH) AF: 0.00758 AC: 443 AN: 58466

GnomAD4 genome AF: 0.00643 AC: 979 AN: 152326 Hom.: 7 Cov.: 33 AF XY: 0.00587 AC XY: 437 AN XY: 74478

African (AFR) AF: 0.00216 AC: 90 AN: 41584

American (AMR) AF: 0.00470 AC: 72 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4828

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 725 AN: 68024

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00906 Hom.: 40

Bravo AF: 0.00645

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.0125 AC: 48

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0117 AC: 100

ExAC AF: 0.00333 AC: 392

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
PhyloP100		2.6
ClinPred		0.032	T
GERP RS		3.7
Varity_R		0.71
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs61757813; hg19: chr7-157333411;