7-157656369-G-T

Variant names:

• chr7-157656369-G-T
• rs140851646
• NM_002847.5:c.2184C>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002847.5(PTPRN2):​c.2184C>A​(p.Gly728Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,550,326 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0080 (55 hom.)
• Consequence: PTPRN2 NM_002847.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.73

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-157656369-G-T is Benign according to our data. Variant chr7-157656369-G-T is described in ClinVar as [Benign]. Clinvar id is 787541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.73 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.2184C>A	p.Gly728Gly	synonymous_variant	Exon 14 of 23	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.2184C>A	p.Gly728Gly	synonymous_variant	Exon 14 of 23	1	NM_002847.5	ENSP00000374069.4
PTPRN2	ENST00000389416.8	c.2133C>A	p.Gly711Gly	synonymous_variant	Exon 13 of 22	1		ENSP00000374067.4
PTPRN2	ENST00000389413.7	c.2097C>A	p.Gly699Gly	synonymous_variant	Exon 13 of 22	1		ENSP00000374064.3
PTPRN2	ENST00000409483.5	c.2070C>A	p.Gly690Gly	synonymous_variant	Exon 13 of 22	2		ENSP00000387114.1

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 718 AN: 152088 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00832

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00425 AC: 665 AN: 156424 AF XY: 0.00441

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.000708

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00391

Gnomad NFE exome AF: 0.00807

Gnomad OTH exome AF: 0.00497

GnomAD4 exome AF: 0.00803 AC: 11225 AN: 1398120 Hom.: 55 Cov.: 31 AF XY: 0.00780 AC XY: 5375 AN XY: 689402

African (AFR) AF: 0.00145 AC: 46 AN: 31622

American (AMR) AF: 0.00190 AC: 68 AN: 35752

Ashkenazi Jewish (ASJ) AF: 0.000358 AC: 9 AN: 25144

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35770

South Asian (SAS) AF: 0.000946 AC: 75 AN: 79248

European-Finnish (FIN) AF: 0.00469 AC: 229 AN: 48822

Middle Eastern (MID) AF: 0.00123 AC: 7 AN: 5690

European-Non Finnish (NFE) AF: 0.00969 AC: 10443 AN: 1078118

Other (OTH) AF: 0.00599 AC: 347 AN: 57954

GnomAD4 genome AF: 0.00472 AC: 718 AN: 152206 Hom.: 6 Cov.: 31 AF XY: 0.00415 AC XY: 309 AN XY: 74386

African (AFR) AF: 0.00152 AC: 63 AN: 41548

American (AMR) AF: 0.00242 AC: 37 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00254 AC: 27 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00832 AC: 566 AN: 68002

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00304 Hom.: 0

Bravo AF: 0.00461

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.2
DANN	Benign	0.86
PhyloP100		1.7
Mutation Taster		=99/1	polymorphism

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

Publications

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Other links and lift over

dbSNP: rs140851646; hg19: chr7-157449061;