12-70745902-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002849.4(PTPRR):c.923G>A(p.Arg308Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: PTPRR NM_002849.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.673

Genes affected

PTPRR (HGNC:9680): (protein tyrosine phosphatase receptor type R) 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 intracellular catalytic domain, and thus represents a receptor-type PTP. Silencing of this gene has been associated with colorectal cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares a symbol (PTPRQ) with another gene, protein tyrosine phosphatase, receptor type, Q (GeneID 374462), which is also located on chromosome 12. [provided by RefSeq, May 2011]

LOC124902960 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036553353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRR	NM_002849.4	c.923G>A	p.Arg308Gln	missense_variant	6/14	ENST00000283228.7
LOC124902960	XR_007063361.1	n.628+26079C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRR	ENST00000283228.7	c.923G>A	p.Arg308Gln	missense_variant	6/14	1	NM_002849.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251256 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135800

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461822 Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11 AN XY: 727206

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

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

Jun 23, 2023

The c.923G>A (p.R308Q) alteration is located in exon 6 (coding exon 6) of the PTPRR gene. This alteration results from a G to A substitution at nucleotide position 923, causing the arginine (R) at amino acid position 308 to be replaced by a glutamine (Q). 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	0.065
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	13
Dann	Benign	0.95
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.037	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.99	N;N;N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.10	N;N;N;N;N;N
REVEL	Benign	0.031
Sift	Benign	0.54	T;T;T;T;T;T
Sift4G	Benign	0.80	T;T;T;T;T;.
Polyphen		0.0060, 0.0010	.;B;B;.;.;.
Vest4		0.11
MutPred		0.35		.;.;Loss of loop (P = 0.0288);.;.;.;
MVP		0.32
MPC		0.13
ClinPred		0.050	T
GERP RS		1.5
Varity_R		0.035
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs756672375; hg19: chr12-71139682;