rs291289

Variant names:

• chr9-10148779-C-T
• rs291289
• NM_002839.4:c.-544-114989G>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.-544-114989G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,954 control chromosomes in the GnomAD database, including 24,043 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 0.54 (24043 hom., cov: 31)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	NM_002839.4	MANE Select	c.-544-114989G>A		intron	N/A	NP_002830.1	P23468-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.-544-114989G>A		intron	N/A	ENSP00000370593.3	P23468-1
	PTPRD	ENST00000463477.5	TSL:1	c.-616-114989G>A		intron	N/A	ENSP00000417661.1	C9J8S8
	PTPRD	ENST00000850942.1		c.-633-46451G>A		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82208 AN: 151836 Hom.: 24058 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.541 AC: 82185 AN: 151954 Hom.: 24043 Cov.: 31 AF XY: 0.537 AC XY: 39908 AN XY: 74264

African (AFR) AF: 0.310 AC: 12854 AN: 41434

American (AMR) AF: 0.535 AC: 8169 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2646 AN: 5162

South Asian (SAS) AF: 0.437 AC: 2102 AN: 4814

European-Finnish (FIN) AF: 0.633 AC: 6691 AN: 10564

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45649 AN: 67940

Other (OTH) AF: 0.565 AC: 1192 AN: 2108

Alfa AF: 0.626 Hom.: 135455

Bravo AF: 0.527

Asia WGS AF: 0.423 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.55
PhyloP100		-1.1
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: rs291289; hg19: chr9-10148779; COSMIC: COSV71773475;