NM_002657.3:c.1340A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002657.3(PLAGL2):​c.1340A>G​(p.Gln447Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PLAGL2
NM_002657.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33
Variant links:
Genes affected
PLAGL2 (HGNC:9047): (PLAG1 like zinc finger 2) Pleiomorphic adenoma gene-like 2 is a zinc-finger protein that recognizes DNA and/or RNA. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.2111493).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLAGL2NM_002657.3 linkc.1340A>G p.Gln447Arg missense_variant Exon 3 of 3 ENST00000246229.5 NP_002648.1 Q9UPG8
PLAGL2XM_005260436.4 linkc.1340A>G p.Gln447Arg missense_variant Exon 3 of 3 XP_005260493.1 Q9UPG8
PLAGL2XM_011528864.3 linkc.1340A>G p.Gln447Arg missense_variant Exon 3 of 3 XP_011527166.1 Q9UPG8
PLAGL2XM_047440200.1 linkc.1340A>G p.Gln447Arg missense_variant Exon 3 of 3 XP_047296156.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLAGL2ENST00000246229.5 linkc.1340A>G p.Gln447Arg missense_variant Exon 3 of 3 1 NM_002657.3 ENSP00000246229.4 Q9UPG8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000548
AC:
1
AN:
182524
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
95924
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000114
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000145
AC:
2
AN:
1382910
Hom.:
0
Cov.:
33
AF XY:
0.00000147
AC XY:
1
AN XY:
680598
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:
0.00000186
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000437
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1340A>G (p.Q447R) alteration is located in exon 3 (coding exon 2) of the PLAGL2 gene. This alteration results from a A to G substitution at nucleotide position 1340, causing the glutamine (Q) at amino acid position 447 to be replaced by an arginine (R). 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
Benign
0.16
BayesDel_addAF
Benign
-0.041
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T
Eigen
Benign
0.063
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.17
N
REVEL
Benign
0.087
Sift
Benign
0.28
T
Sift4G
Benign
0.54
T
Polyphen
0.90
P
Vest4
0.089
MutPred
0.15
Loss of helix (P = 0.0237);
MVP
0.64
MPC
1.5
ClinPred
0.35
T
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1345662604; hg19: chr20-30784406; API