Genetic Variant NM_002839.4:c.5534+34G>A (chr9-8331548-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002839.4(PTPRD):c.5534+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 1,028,882 control chromosomes in the GnomAD database, including 2,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 170 hom., cov: 32)

Exomes 𝑓: 0.070 ( 2174 hom. )

Consequence

PTPRD
NM_002839.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.92

Publications

3 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 9-8331548-C-T is Benign according to our data. Variant chr9-8331548-C-T is described in ClinVar as [Benign]. Clinvar id is 1247371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRD	NM_002839.4 link	c.5534+34G>A		intron_variant	Intron 44 of 45	ENST00000381196.9	NP_002830.1	P23468-1Q2HXI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRD	ENST00000381196.9 link	c.5534+34G>A		intron_variant	Intron 44 of 45	5	NM_002839.4	ENSP00000370593.3		P23468-1

Frequencies

GnomAD3 genomes

AF:

0.0499

AC:

5690

AN:

114118

Hom.:

171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.0430

Gnomad AMR

AF:

0.0636

Gnomad ASJ

AF:

0.0462

Gnomad EAS

AF:

0.0394

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.0541

Gnomad MID

AF:

0.0667

Gnomad NFE

AF:

0.0476

Gnomad OTH

AF:

0.0547

GnomAD2 exomes

AF:

0.0823

AC:

12513

AN:

152068

AF XY:

0.0898

show subpopulations

Gnomad AFR exome

AF:

0.0387

Gnomad AMR exome

AF:

0.0996

Gnomad ASJ exome

AF:

0.0517

Gnomad EAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0616

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0797

GnomAD4 exome

AF:

0.0704

AC:

64408

AN:

914726

Hom.:

2174

Cov.:

AF XY:

0.0753

AC XY:

34457

AN XY:

457470

show subpopulations

African (AFR)

AF:

0.0404

AC:

302

AN:

7478

American (AMR)

AF:

0.116

AC:

2300

AN:

19820

Ashkenazi Jewish (ASJ)

AF:

0.0522

AC:

799

AN:

15316

East Asian (EAS)

AF:

0.0655

AC:

1328

AN:

20266

South Asian (SAS)

AF:

0.232

AC:

11930

AN:

51460

European-Finnish (FIN)

AF:

0.0627

AC:

2517

AN:

40168

Middle Eastern (MID)

AF:

0.127

AC:

451

AN:

3558

European-Non Finnish (NFE)

AF:

0.0582

AC:

41888

AN:

719484

Other (OTH)

AF:

0.0778

AC:

2893

AN:

37176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

2263

4525

6788

9050

11313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0500

AC:

5704

AN:

114156

Hom.:

170

Cov.:

AF XY:

0.0544

AC XY:

3030

AN XY:

55738

show subpopulations

African (AFR)

AF:

0.0222

AC:

456

AN:

20574

American (AMR)

AF:

0.0638

AC:

731

AN:

11450

Ashkenazi Jewish (ASJ)

AF:

0.0462

AC:

131

AN:

2836

East Asian (EAS)

AF:

0.0394

AC:

154

AN:

3906

South Asian (SAS)

AF:

0.196

AC:

755

AN:

3860

European-Finnish (FIN)

AF:

0.0541

AC:

499

AN:

9216

Middle Eastern (MID)

AF:

0.0696

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.0476

AC:

2834

AN:

59588

Other (OTH)

AF:

0.0555

AC:

AN:

1658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

279

558

837

1116

1395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0383

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.0890

AC:

307

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 29, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.10

(source)

DANN

Benign

0.32

PhyloP100

-1.9

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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NM_002839.4:c.5534+34G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over