Genetic Variant ENST00000308354.11:c.23C>G (chr8-22578802-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000308354.11(PDLIM2):c.23C>G(p.Pro8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,081,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PDLIM2
ENST00000308354.11 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.451

Publications

0 publications found

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]

PDLIM2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12223011).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000308354.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM2	NM_021630.6		c.23C>G	p.Pro8Arg	missense	Exon 1 of 10	NP_067643.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDLIM2	ENST00000308354.11	TSL:1	c.23C>G	p.Pro8Arg	missense	Exon 1 of 10	ENSP00000312634.7	Q96JY6-5
PDLIM2	ENST00000339162.11	TSL:1	c.23C>G	p.Pro8Arg	missense	Exon 1 of 10	ENSP00000342035.8	Q96JY6-5
PDLIM2	ENST00000884623.1		c.-3+669C>G		intron	N/A	ENSP00000554682.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1081994

Hom.:

Cov.:

AF XY:

0.00000196

AC XY:

AN XY:

511060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23026

American (AMR)

AF:

0.00

AC:

AN:

8424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14384

East Asian (EAS)

AF:

0.00

AC:

AN:

26528

South Asian (SAS)

AF:

0.00

AC:

AN:

19610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21112

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4482

European-Non Finnish (NFE)

AF:

0.00000217

AC:

AN:

920572

Other (OTH)

AF:

0.0000228

AC:

AN:

43856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.7

(source)

DANN

Benign

0.79

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.32

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.98

PhyloP100

-0.45

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.020

REVEL

Benign

0.012

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.21

MutPred

0.18

Gain of helix (P = 0.005)

MVP

0.33

MPC

0.079

ClinPred

0.076

GERP RS

-1.9

PromoterAI

0.023

Neutral

(source)

gMVP

0.088

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over