9-8376609-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002839.4(PTPRD):ā€‹c.4504A>Cā€‹(p.Lys1502Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000335 in 1,612,588 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000035 ( 0 hom. )

Consequence

PTPRD
NM_002839.4 missense, splice_region

Scores

2
8
8
Splicing: ADA: 0.7515
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 51 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTPRDNM_002839.4 linkuse as main transcriptc.4504A>C p.Lys1502Gln missense_variant, splice_region_variant 38/46 ENST00000381196.9 NP_002830.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTPRDENST00000381196.9 linkuse as main transcriptc.4504A>C p.Lys1502Gln missense_variant, splice_region_variant 38/465 NM_002839.4 ENSP00000370593 P1P23468-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152000
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000160
AC:
4
AN:
250638
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135452
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000349
AC:
51
AN:
1460588
Hom.:
0
Cov.:
31
AF XY:
0.0000358
AC XY:
26
AN XY:
726594
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152000
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74224
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 26, 2022The c.4504A>C (p.K1502Q) alteration is located in exon 38 (coding exon 27) of the PTPRD gene. This alteration results from a A to C substitution at nucleotide position 4504, causing the lysine (K) at amino acid position 1502 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.51
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.62
D;.;.;.;.;D;D;.;.
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.52
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;.;.;.;.;L;L;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-3.1
D;D;D;.;D;D;D;D;D
REVEL
Benign
0.19
Sift
Uncertain
0.0020
D;D;T;.;D;D;D;D;D
Sift4G
Benign
0.14
T;T;T;T;T;T;T;T;T
Polyphen
0.62
P;.;.;P;.;P;P;.;.
Vest4
0.65
MVP
0.35
ClinPred
0.81
D
GERP RS
5.6
Varity_R
0.72
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.75
dbscSNV1_RF
Benign
0.52
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.

Other links and lift over

dbSNP: rs144200611; hg19: chr9-8376609; API