rs2819332

Variant names:

• chr1-43539609-G-A
• rs2819332
• NM_002840.5:c.-46+1332G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002840.5(PTPRF):​c.-46+1332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,120 control chromosomes in the GnomAD database, including 4,086 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4086 hom., cov: 32)
• Consequence: PTPRF NM_002840.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 17 publications found

Genes affected

PTPRF (HGNC:9670): (protein tyrosine phosphatase receptor type F) 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 two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region contains three Ig-like domains, and nine non-Ig like domains similar to that of neural-cell adhesion molecule. This PTP was shown to function in the regulation of epithelial cell-cell contacts at adherents junctions, as well as in the control of beta-catenin signaling. An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

PTPRF Gene-Disease associations (from GenCC):

• breasts and/or nipples, aplasia or hypoplasia of, 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRF	NM_002840.5	c.-46+1332G>A		intron_variant	Intron 2 of 33	ENST00000359947.9	NP_002831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRF	ENST00000359947.9	c.-46+1332G>A		intron_variant	Intron 2 of 33	1	NM_002840.5	ENSP00000353030.4

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31752 AN: 152002 Hom.: 4085 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.209 AC: 31763 AN: 152120 Hom.: 4086 Cov.: 32 AF XY: 0.216 AC XY: 16046 AN XY: 74354

African (AFR) AF: 0.0652 AC: 2709 AN: 41532

American (AMR) AF: 0.368 AC: 5626 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3472

East Asian (EAS) AF: 0.236 AC: 1222 AN: 5168

South Asian (SAS) AF: 0.396 AC: 1907 AN: 4814

European-Finnish (FIN) AF: 0.225 AC: 2378 AN: 10584

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16165 AN: 67964

Other (OTH) AF: 0.216 AC: 457 AN: 2112

Alfa AF: 0.235 Hom.: 5505

Bravo AF: 0.208

Asia WGS AF: 0.309 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.44
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2819332; hg19: chr1-44005280;