9-10430602-T-C

Variant names:

• chr9-10430602-T-C
• rs649891
• NM_002839.4:c.-599-89585A>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.-599-89585A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,740 control chromosomes in the GnomAD database, including 14,724 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 0.37 (14724 hom., cov: 32)
• Consequence: PTPRD NM_002839.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 30 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 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.-599-89585A>G		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.-599-89585A>G		intron	N/A	ENSP00000370593.3	P23468-1
	PTPRD	ENST00000463477.5	TSL:1	c.-671-89585A>G		intron	N/A	ENSP00000417661.1	C9J8S8
	PTPRD	ENST00000850942.1		c.-760-89585A>G		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56618 AN: 151624 Hom.: 14679 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.374 AC: 56721 AN: 151740 Hom.: 14724 Cov.: 32 AF XY: 0.379 AC XY: 28084 AN XY: 74118

African (AFR) AF: 0.677 AC: 28033 AN: 41428

American (AMR) AF: 0.455 AC: 6892 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3883 AN: 5134

South Asian (SAS) AF: 0.440 AC: 2121 AN: 4816

European-Finnish (FIN) AF: 0.176 AC: 1858 AN: 10576

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.178 AC: 12063 AN: 67846

Other (OTH) AF: 0.348 AC: 732 AN: 2104

Alfa AF: 0.247 Hom.: 26088

Bravo AF: 0.409

Asia WGS AF: 0.587 AC: 2012 AN: 3434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.38
PhyloP100		-0.12
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: rs649891; hg19: chr9-10430602;