Genetic Variant PTPRD:c.-104+18664G>T (chr9-9000033-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002839.4(PTPRD):c.-104+18664G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,826 control chromosomes in the GnomAD database, including 17,526 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 0.46 ( 17526 hom., cov: 32)

Consequence

PTPRD
NM_002839.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.509

Publications

2 publications found

Variant links:

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]

PTPRD links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 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.-104+18664G>T		intron	N/A	NP_002830.1	P23468-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTPRD	ENST00000381196.9	TSL:5 MANE Select	c.-104+18664G>T	intron	N/A	ENSP00000370593.3	P23468-1
PTPRD	ENST00000463477.5	TSL:1	c.-104+18664G>T	intron	N/A	ENSP00000417661.1	C9J8S8
PTPRD	ENST00000850942.1		c.-104+18664G>T	intron	N/A	ENSP00000521027.1

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70091

AN:

151710

Hom.:

17495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.337

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.664

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.381

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.426

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

GnomAD4 genome

AF:

0.462

AC:

70171

AN:

151826

Hom.:

17526

Cov.:

AF XY:

0.466

AC XY:

34565

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.618

AC:

25581

AN:

41410

American (AMR)

AF:

0.570

AC:

8677

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1475

AN:

3464

East Asian (EAS)

AF:

0.665

AC:

3418

AN:

5142

South Asian (SAS)

AF:

0.446

AC:

2146

AN:

4814

European-Finnish (FIN)

AF:

0.381

AC:

4012

AN:

10544

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23524

AN:

67908

Other (OTH)

AF:

0.426

AC:

898

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1837

3673

5510

7346

9183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.388

Hom.:

54529

Bravo

AF:

0.484

Asia WGS

AF:

0.519

AC:

1803

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.0

(source)

DANN

Benign

0.63

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over