9-9969023-C-G

Variant summary

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

The NM_002839.4(PTPRD):c.-471-30413G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,950 control chromosomes in the GnomAD database, including 33,332 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 0.63 (33332 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4	c.-471-30413G>C		intron_variant		ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9	c.-471-30413G>C		intron_variant		5	NM_002839.4	P1
PTPRD	ENST00000463477.5	c.-543-30413G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96377 AN: 151834 Hom.: 33272 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.635 AC: 96488 AN: 151950 Hom.: 33332 Cov.: 31 AF XY: 0.633 AC XY: 47043 AN XY: 74264

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.632

Alfa AF: 0.380 Hom.: 877

Bravo AF: 0.655

Asia WGS AF: 0.794 AC: 2761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.42
Dann	Benign	0.24

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: rs4742645; hg19: chr9-9969023; COSMIC: COSV67006349;