20-32197011-G-C

Variant names:

• chr20-32197011-G-C
• rs2047233037
• NM_002657.3:c.932C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002657.3(PLAGL2):​c.932C>G​(p.Pro311Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 0.0000055 (0 hom.)
• Consequence: PLAGL2 NM_002657.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.15

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAGL2	NM_002657.3	c.932C>G	p.Pro311Arg	missense_variant	Exon 3 of 3	ENST00000246229.5	NP_002648.1
PLAGL2	XM_005260436.4	c.932C>G	p.Pro311Arg	missense_variant	Exon 3 of 3		XP_005260493.1
PLAGL2	XM_011528864.3	c.932C>G	p.Pro311Arg	missense_variant	Exon 3 of 3		XP_011527166.1
PLAGL2	XM_047440200.1	c.932C>G	p.Pro311Arg	missense_variant	Exon 3 of 3		XP_047296156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAGL2	ENST00000246229.5	c.932C>G	p.Pro311Arg	missense_variant	Exon 3 of 3	1	NM_002657.3	ENSP00000246229.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461692 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727166

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: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.932C>G (p.P311R) alteration is located in exon 3 (coding exon 2) of the PLAGL2 gene. This alteration results from a C to G substitution at nucleotide position 932, causing the proline (P) at amino acid position 311 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	0.26
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.084
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0043	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.16
Sift	Benign	0.086	T
Sift4G	Benign	0.13	T
Polyphen		0.010	B
Vest4		0.62
MutPred		0.25		Gain of catalytic residue at P311 (P = 0.0089);
MVP		0.28
MPC		0.72
ClinPred		0.57	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2047233037; hg19: chr20-30784814;