rs1359114

Positions:

• chr9-8423958-C-G
• chr9-8423958-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002839.4(PTPRD):​c.4086+12634G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,832 control chromosomes in the GnomAD database, including 19,171 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 0.50 (19171 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.4086+12634G>C		intron_variant		ENST00000381196.9	NP_002830.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9	c.4086+12634G>C		intron_variant		5	NM_002839.4	ENSP00000370593	P1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75333 AN: 151714 Hom.: 19132 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.497 AC: 75426 AN: 151832 Hom.: 19171 Cov.: 32 AF XY: 0.503 AC XY: 37265 AN XY: 74146

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.498

Alfa AF: 0.482 Hom.: 2226

Bravo AF: 0.500

Asia WGS AF: 0.657 AC: 2282 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs1359114; hg19: chr9-8423958; COSMIC: COSV61954728;