1-19978381-G-C

Variant names:

• chr1-19978381-G-C
• NM_001395463.1:c.184C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001395463.1(PLA2G2A):​c.184C>G​(p.Arg62Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R62C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLA2G2A NM_001395463.1 missense, splice_region
• Scores: Splicing: ADA: 0.002453
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.99

Genes affected

PLA2G2A (HGNC:9031): (phospholipase A2 group IIA) The protein encoded by this gene is a member of the phospholipase A2 family (PLA2). PLA2s constitute a diverse family of enzymes with respect to sequence, function, localization, and divalent cation requirements. This gene product belongs to group II, which contains secreted form of PLA2, an extracellular enzyme that has a low molecular mass and requires calcium ions for catalysis. It catalyzes the hydrolysis of the sn-2 fatty acid acyl ester bond of phosphoglycerides, releasing free fatty acids and lysophospholipids, and thought to participate in the regulation of the phospholipid metabolism in biomembranes. Several alternatively spliced transcript variants with different 5' UTRs have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2A	NM_001395463.1	c.184C>G	p.Arg62Gly	missense_variant, splice_region_variant	Exon 3 of 5	ENST00000482011.3	NP_001382392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2A	ENST00000482011.3	c.184C>G	p.Arg62Gly	missense_variant, splice_region_variant	Exon 3 of 5	1	NM_001395463.1	ENSP00000504762.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459794 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 726226

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.012
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	.;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Uncertain	0.89	D;D;.
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	4.1	.;H;H
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-4.4	.;D;D
REVEL	Benign	0.20
Sift	Benign	0.10	.;T;T
Sift4G	Benign	0.10	.;T;T
Polyphen		0.98	.;D;D
Vest4		0.46, 0.46
MutPred		0.79		.;Loss of phosphorylation at T60 (P = 0.1283);Loss of phosphorylation at T60 (P = 0.1283);
MVP		0.44
MPC		1.6
ClinPred		0.86	D
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0025
dbscSNV1_RF	Benign	0.33
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-20304874;