NM_002839.4:c.-545+80700G>A

Variant names:

• chr9-10260263-C-T
• rs2475335
• NM_002839.4:c.-545+80700G>A

Variant summary

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

The NM_002839.4(PTPRD):​c.-545+80700G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,032 control chromosomes in the GnomAD database, including 40,872 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 0.72 (40872 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 22 publications found

Genes affected

PTPRD (HGNC:9668): (protein tyrosine phosphatase receptor type D) 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 contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chicken and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple alternatively spliced transcript variants of this gene have been reported. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jan 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-545+80700G>A		intron_variant	Intron 3 of 45	ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.-545+80700G>A		intron_variant	Intron 3 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-617+80700G>A		intron_variant	Intron 3 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-705-60770G>A		intron_variant	Intron 3 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109846 AN: 151914 Hom.: 40851 Cov.: 31

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.815

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.723 AC: 109914 AN: 152032 Hom.: 40872 Cov.: 31 AF XY: 0.725 AC XY: 53860 AN XY: 74332

African (AFR) AF: 0.539 AC: 22322 AN: 41432

American (AMR) AF: 0.713 AC: 10901 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2687 AN: 3468

East Asian (EAS) AF: 0.779 AC: 4024 AN: 5166

South Asian (SAS) AF: 0.726 AC: 3500 AN: 4818

European-Finnish (FIN) AF: 0.815 AC: 8616 AN: 10574

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55398 AN: 67974

Other (OTH) AF: 0.726 AC: 1535 AN: 2114

Alfa AF: 0.776 Hom.: 149551

Bravo AF: 0.707

Asia WGS AF: 0.719 AC: 2500 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.51
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2475335; hg19: chr9-10260263;