9-8319890-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_002839.4(PTPRD):​c.5611G>C​(p.Asp1871His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PTPRD
NM_002839.4 missense

Scores

14
2
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTPRDNM_002839.4 linkuse as main transcriptc.5611G>C p.Asp1871His missense_variant 45/46 ENST00000381196.9 NP_002830.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTPRDENST00000381196.9 linkuse as main transcriptc.5611G>C p.Asp1871His missense_variant 45/465 NM_002839.4 ENSP00000370593 P1P23468-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 GeneticsAug 21, 2023The c.5611G>C (p.D1871H) alteration is located in exon 45 (coding exon 34) of the PTPRD gene. This alteration results from a G to C substitution at nucleotide position 5611, causing the aspartic acid (D) at amino acid position 1871 to be replaced by a histidine (H). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.91
D;.;.;.;.;D;D;.;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.97
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.95
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Pathogenic
3.4
M;.;.;.;.;M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-6.3
D;D;D;.;D;D;D;D;D
REVEL
Pathogenic
0.66
Sift
Pathogenic
0.0
D;D;D;.;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;.;D;.;D;D;.;.
Vest4
0.96
MutPred
0.84
Gain of MoRF binding (P = 0.0471);.;.;.;.;Gain of MoRF binding (P = 0.0471);Gain of MoRF binding (P = 0.0471);.;.;
MVP
0.70
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.89
gMVP
0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-8319890; COSMIC: COSV61933475; API