Variant 9-8331644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002839.4(PTPRD):c.5472C>T(p.Ile1824=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,613,714 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

PTPRD
NM_002839.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.86

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 9-8331644-G-A is Benign according to our data. Variant chr9-8331644-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 734322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.87 with no splicing effect.

BS2

High AC in GnomAd4 at 216 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRD	NM_002839.4 linkuse as main transcript	c.5472C>T	p.Ile1824=	synonymous_variant	44/46	ENST00000381196.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRD	ENST00000381196.9 linkuse as main transcript	c.5472C>T	p.Ile1824=	synonymous_variant	44/46	5	NM_002839.4	P1	P23468-1

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

217

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000920

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00231

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00148

AC:

371

AN:

250524

Hom.:

AF XY:

0.00145

AC XY:

196

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000522

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000653

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00250

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00225

AC:

3293

AN:

1461714

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1617

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.000454

Gnomad4 SAS exome

AF:

0.00122

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.00268

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00142

AC:

216

AN:

152000

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000894

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00231

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00139

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00279

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	PTPRD: BP4, BP7 -

PTPRD-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.4

DANN

Benign

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over