8-22578982-C-T

Variant names:

• chr8-22578982-C-T
• ENST00000308354.11:c.203C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021630.6(PDLIM2):​c.203C>T​(p.Pro68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: PDLIM2 NM_021630.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.302

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.107792765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDLIM2	NM_021630.6	c.203C>T	p.Pro68Leu	missense_variant	Exon 1 of 10		NP_067643.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDLIM2	ENST00000308354.11	c.203C>T	p.Pro68Leu	missense_variant	Exon 1 of 10	1		ENSP00000312634.7
PDLIM2	ENST00000339162.11	c.203C>T	p.Pro68Leu	missense_variant	Exon 1 of 10	1		ENSP00000342035.8
PDLIM2	ENST00000456545.5	c.-3+655C>T		intron_variant	Intron 1 of 7	5		ENSP00000401992.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.18e-7 AC: 1 AN: 1089630 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 514860

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.203C>T (p.P68L) 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 203, causing the proline (P) at amino acid position 68 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	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.1
DANN	Benign	0.80
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.44	T;.
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.25	.;N
REVEL	Benign	0.019
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.0080	D;D
Vest4		0.078
MutPred		0.14		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.34
MPC		0.37
ClinPred		0.35	T
GERP RS		1.5
gMVP		0.094

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: chr8-22436495;