NM_002839.4:c.-286-14043A>C

Variant names:

• chr9-9588824-T-G
• rs598356
• NM_002839.4:c.-286-14043A>C

Variant summary

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

The NM_002839.4(PTPRD):​c.-286-14043A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,746 control chromosomes in the GnomAD database, including 7,876 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 0.31 (7876 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 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.-286-14043A>C		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.-286-14043A>C		intron	N/A	ENSP00000370593.3
	PTPRD	ENST00000463477.5	TSL:1	c.-358-14043A>C		intron	N/A	ENSP00000417661.1
	PTPRD	ENST00000850942.1		c.-286-14043A>C		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47497 AN: 151628 Hom.: 7872 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.313 AC: 47526 AN: 151746 Hom.: 7876 Cov.: 32 AF XY: 0.311 AC XY: 23042 AN XY: 74142

African (AFR) AF: 0.262 AC: 10865 AN: 41468

American (AMR) AF: 0.252 AC: 3832 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3470

East Asian (EAS) AF: 0.180 AC: 927 AN: 5142

South Asian (SAS) AF: 0.152 AC: 735 AN: 4820

European-Finnish (FIN) AF: 0.407 AC: 4285 AN: 10538

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24747 AN: 67802

Other (OTH) AF: 0.316 AC: 664 AN: 2102

Alfa AF: 0.336 Hom.: 4198

Bravo AF: 0.300

Asia WGS AF: 0.202 AC: 696 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.41
PhyloP100		0.051
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: rs598356; hg19: chr9-9588824; COSMIC: COSV67064896;