8-22579381-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000397760(PDLIM2):​c.-149C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,500,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

PDLIM2
ENST00000397760 5_prime_UTR_premature_start_codon_gain

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.576
Variant links:
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.061291218).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDLIM2NM_021630.6 linkc.602C>T p.Pro201Leu missense_variant Exon 1 of 10 NP_067643.3 Q96JY6-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDLIM2ENST00000397760 linkc.-149C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 10 1 ENSP00000380867.4 Q96JY6-1
PDLIM2ENST00000308354.11 linkc.602C>T p.Pro201Leu missense_variant Exon 1 of 10 1 ENSP00000312634.7 Q96JY6-5
PDLIM2ENST00000339162.11 linkc.602C>T p.Pro201Leu missense_variant Exon 1 of 10 1 ENSP00000342035.8 Q96JY6-5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000260
AC:
35
AN:
1347870
Hom.:
0
Cov.:
32
AF XY:
0.0000256
AC XY:
17
AN XY:
664062
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000282
Gnomad4 OTH exome
AF:
0.0000889
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152214
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000436
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000728
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.602C>T (p.P201L) alteration is located in exon 1 (coding exon 1) of the PDLIM2 gene. This alteration results from a C to T substitution at nucleotide position 602, causing the proline (P) at amino acid position 201 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
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
2.2
DANN
Benign
0.88
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.37
T;.
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.061
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.14
.;N
REVEL
Benign
0.012
Sift
Uncertain
0.0010
.;D
Sift4G
Uncertain
0.0050
D;D
Vest4
0.036
MutPred
0.24
Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP
0.21
MPC
0.080
ClinPred
0.064
T
GERP RS
-9.1
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs748827218; hg19: chr8-22436894; API