1-43547684-G-C

Variant names:

• chr1-43547684-G-C
• rs2782641
• NM_002840.5:c.91+2518G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002840.5(PTPRF):​c.91+2518G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: PTPRF NM_002840.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657
• Publications: 21 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: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002840.5. 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
	PTPRF	NM_002840.5	MANE Select	c.91+2518G>C		intron	N/A	NP_002831.2	P10586-1
	PTPRF	NM_130440.4		c.91+2518G>C		intron	N/A	NP_569707.2	P10586-2
	PTPRF	NM_001329138.2		c.91+2518G>C		intron	N/A	NP_001316067.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRF	ENST00000359947.9	TSL:1 MANE Select	c.91+2518G>C		intron	N/A	ENSP00000353030.4	P10586-1
	PTPRF	ENST00000438120.5	TSL:1	c.91+2518G>C		intron	N/A	ENSP00000398822.1	P10586-2
	PTPRF	ENST00000437607.1	TSL:1	c.91+2518G>C		intron	N/A	ENSP00000413306.1	A2A437

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
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.79
PhyloP100		0.66

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: rs2782641; hg19: chr1-44013355;