9-9581692-C-T

Variant names:

• chr9-9581692-C-T
• rs668026
• NM_002839.4:c.-286-6911G>A

Variant summary

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

The ENST00000381196.9(PTPRD):​c.-286-6911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,942 control chromosomes in the GnomAD database, including 8,008 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 0.32 (8008 hom., cov: 32)
• Consequence: PTPRD ENST00000381196.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381196.9. 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.-286-6911G>A		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.-286-6911G>A		intron	N/A	ENSP00000370593.3
	PTPRD	ENST00000463477.5	TSL:1	c.-358-6911G>A		intron	N/A	ENSP00000417661.1
	PTPRD	ENST00000850942.1		c.-286-6911G>A		intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48155 AN: 151824 Hom.: 7983 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.317 AC: 48215 AN: 151942 Hom.: 8008 Cov.: 32 AF XY: 0.317 AC XY: 23535 AN XY: 74252

African (AFR) AF: 0.379 AC: 15717 AN: 41452

American (AMR) AF: 0.244 AC: 3716 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3468

East Asian (EAS) AF: 0.182 AC: 938 AN: 5168

South Asian (SAS) AF: 0.107 AC: 515 AN: 4828

European-Finnish (FIN) AF: 0.402 AC: 4242 AN: 10550

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20924 AN: 67902

Other (OTH) AF: 0.318 AC: 672 AN: 2112

Alfa AF: 0.256 Hom.: 1157

Bravo AF: 0.309

Asia WGS AF: 0.193 AC: 668 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.60
DANN	Benign	0.71
PhyloP100		-0.30
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: rs668026; hg19: chr9-9581692; COSMIC: COSV67064866;