9-10318490-G-T

Variant names:

• chr9-10318490-G-T
• rs587791
• NM_002839.4:c.-545+22473C>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+22473C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,908 control chromosomes in the GnomAD database, including 7,825 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 0.29 (7825 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4	c.-545+22473C>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+22473C>A		intron_variant	Intron 3 of 45	5	NM_002839.4	ENSP00000370593.3
PTPRD	ENST00000463477.5	c.-617+22473C>A		intron_variant	Intron 3 of 16	1		ENSP00000417661.1
PTPRD	ENST00000850942.1	c.-706+22473C>A		intron_variant	Intron 3 of 47			ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43361 AN: 151790 Hom.: 7807 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.286 AC: 43434 AN: 151908 Hom.: 7825 Cov.: 32 AF XY: 0.286 AC XY: 21202 AN XY: 74224

African (AFR) AF: 0.506 AC: 20963 AN: 41430

American (AMR) AF: 0.332 AC: 5065 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3472

East Asian (EAS) AF: 0.159 AC: 814 AN: 5128

South Asian (SAS) AF: 0.284 AC: 1372 AN: 4824

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10574

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11936 AN: 67930

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.215 Hom.: 13076

Bravo AF: 0.305

Asia WGS AF: 0.292 AC: 1015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.27
PhyloP100		-0.14
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: rs587791; hg19: chr9-10318490;