9-9020223-T-C

Variant names:

• chr9-9020223-T-C
• rs378363
• NM_002839.4:c.-142-1488A>G

Variant summary

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

The NM_002839.4(PTPRD):​c.-142-1488A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,104 control chromosomes in the GnomAD database, including 4,029 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 0.23 (4029 hom., cov: 33)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591
• Publications: 7 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002839.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	NM_002839.4	MANE Select	c.-142-1488A>G		intron	N/A	NP_002830.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.-142-1488A>G		intron	N/A	ENSP00000370593.3
	PTPRD	ENST00000463477.5	TSL:1	c.-142-1488A>G		intron	N/A	ENSP00000417661.1
	PTPRD	ENST00000850942.1		c.-142-1488A>G		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34428 AN: 151986 Hom.: 4025 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.226 AC: 34444 AN: 152104 Hom.: 4029 Cov.: 33 AF XY: 0.221 AC XY: 16460 AN XY: 74366

African (AFR) AF: 0.260 AC: 10799 AN: 41494

American (AMR) AF: 0.181 AC: 2755 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3470

East Asian (EAS) AF: 0.164 AC: 851 AN: 5180

South Asian (SAS) AF: 0.165 AC: 796 AN: 4820

European-Finnish (FIN) AF: 0.188 AC: 1990 AN: 10582

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16052 AN: 67978

Other (OTH) AF: 0.215 AC: 455 AN: 2112

Alfa AF: 0.232 Hom.: 13465

Bravo AF: 0.225

Asia WGS AF: 0.190 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.1
DANN	Benign	0.88
PhyloP100		0.59
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: rs378363; hg19: chr9-9020223;