9-8376669-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002839.4(PTPRD):ā€‹c.4444G>Cā€‹(p.Val1482Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PTPRD
NM_002839.4 missense

Scores

3
12
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.72
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTPRDNM_002839.4 linkuse as main transcriptc.4444G>C p.Val1482Leu missense_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.4444G>C p.Val1482Leu missense_variant 38/465 NM_002839.4 ENSP00000370593 P1P23468-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1460928
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726782
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 GeneticsMar 04, 2024The c.4444G>C (p.V1482L) alteration is located in exon 38 (coding exon 27) of the PTPRD gene. This alteration results from a G to C substitution at nucleotide position 4444, causing the valine (V) at amino acid position 1482 to be replaced by a leucine (L). 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
0.68
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.76
D;.;.;.;.;D;D;.;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.62
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.3
M;.;.;.;.;M;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-2.7
D;D;D;.;D;D;D;D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0020
D;D;D;.;D;D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D;D;D;D;D;D
Polyphen
0.48
P;.;.;B;.;P;P;.;.
Vest4
0.75
MutPred
0.75
Loss of sheet (P = 0.0817);.;.;.;.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;.;
MVP
0.49
ClinPred
0.96
D
GERP RS
5.6
Varity_R
0.62
gMVP
0.65

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: chr9-8376669; API