9-8341267-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_002839.4(PTPRD):c.4949G>A(p.Arg1650His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 1,584,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
PTPRD
NM_002839.4 missense, splice_region
NM_002839.4 missense, splice_region
Scores
3
8
7
Splicing: ADA: 0.9860
2
Clinical Significance
Conservation
PhyloP100: 7.57
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPRD | NM_002839.4 | c.4949G>A | p.Arg1650His | missense_variant, splice_region_variant | 41/46 | ENST00000381196.9 | NP_002830.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPRD | ENST00000381196.9 | c.4949G>A | p.Arg1650His | missense_variant, splice_region_variant | 41/46 | 5 | NM_002839.4 | ENSP00000370593 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000465 AC: 7AN: 150634Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000539 AC: 12AN: 222508Hom.: 0 AF XY: 0.0000580 AC XY: 7AN XY: 120684
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GnomAD4 exome AF: 0.0000286 AC: 41AN: 1433506Hom.: 0 Cov.: 30 AF XY: 0.0000253 AC XY: 18AN XY: 712084
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GnomAD4 genome AF: 0.0000464 AC: 7AN: 150734Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73536
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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 submitter | clinical testing | Ambry Genetics | Feb 28, 2023 | The c.4949G>A (p.R1650H) alteration is located in exon 41 (coding exon 30) of the PTPRD gene. This alteration results from a G to A substitution at nucleotide position 4949, causing the arginine (R) at amino acid position 1650 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.;.;.;D;D;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;L;L;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;.;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;T;T;.;T;D;D;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
B;.;.;D;.;B;B;.;.
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at