8-22580629-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001368120.1(PDLIM2):c.25G>A(p.Gly9Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
PDLIM2
NM_001368120.1 missense
NM_001368120.1 missense
Scores
6
5
7
Clinical Significance
Conservation
PhyloP100: 6.03
Genes affected
PDLIM2 (HGNC:13992): (PDZ and LIM domain 2) This gene encodes a member of the ALP subfamily of PDZ-LIM domain proteins. The encoded protein suppresses anchorage-dependent growth and promotes cell migration and adhesion through interactions with the actin cytoskeleton via the PDZ domain. The encoded protein is also a putative tumor suppressor protein, and decreased expression of this gene is associated with several malignancies including breast cancer and adult T-cell leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.8
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDLIM2 | NM_001368120.1 | c.25G>A | p.Gly9Arg | missense_variant | 1/9 | ENST00000409417.6 | |
PDLIM2 | NM_021630.6 | c.775G>A | p.Gly259Arg | missense_variant | 2/10 | ||
PDLIM2 | NM_176871.5 | c.25G>A | p.Gly9Arg | missense_variant | 1/10 | ||
PDLIM2 | NM_198042.4 | c.25G>A | p.Gly9Arg | missense_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM2 | ENST00000409417.6 | c.25G>A | p.Gly9Arg | missense_variant | 1/9 | 1 | NM_001368120.1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250842Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135768
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461754Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727166
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
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1
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0
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 05, 2024 | The c.775G>A (p.G259R) alteration is located in exon 2 (coding exon 2) of the PDLIM2 gene. This alteration results from a G to A substitution at nucleotide position 775, causing the glycine (G) at amino acid position 259 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
DEOGEN2
Benign
T;.;.;T;D;D;T;T;T;T;T;.;.;D
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D;.;.;.;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D;D;D;.;D;D;D;.;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;.;D;D;D;D;.;D;D;D;.;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;.;D;D;D;D;D;D;D
Polyphen
1.0, 0.98
.;.;.;D;D;D;.;.;.;.;.;D;D;D
Vest4
0.84, 0.84, 0.85, 0.64, 0.63, 0.56, 0.86, 0.84
MutPred
Gain of MoRF binding (P = 0.024);.;.;Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);Gain of MoRF binding (P = 0.024);
MVP
MPC
0.47
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at