1-20116342-G-A

Variant names:

• chr1-20116342-G-A
• rs1399134237
• NM_012400.4:c.176C>T

Variant summary

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

The NM_012400.4(PLA2G2D):​c.176C>T​(p.Ala59Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PLA2G2D NM_012400.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.20

Genes affected

PLA2G2D (HGNC:9033): (phospholipase A2 group IID) This gene encodes a secreted member of the phospholipase A2 family, and is found in a cluster of related family members on chromosome 1. Phospholipase A2 family members hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce lysophospholipids and free fatty acid. This gene may be involved in inflammation and immune response, and in weight loss associated with chronic obstructive pulmonary disease. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2D	NM_012400.4	c.176C>T	p.Ala59Val	missense_variant	Exon 2 of 4	ENST00000375105.8	NP_036532.1
PLA2G2D	NM_001271814.2	c.176C>T	p.Ala59Val	missense_variant	Exon 2 of 3		NP_001258743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2D	ENST00000375105.8	c.176C>T	p.Ala59Val	missense_variant	Exon 2 of 4	1	NM_012400.4	ENSP00000364246.3
PLA2G2D	ENST00000617227.1	c.176C>T	p.Ala59Val	missense_variant	Exon 2 of 3	1		ENSP00000482871.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251398 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135880

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461772 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727192

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: 0.0000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

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.176C>T (p.A59V) alteration is located in exon 2 (coding exon 2) of the PLA2G2D gene. This alteration results from a C to T substitution at nucleotide position 176, causing the alanine (A) at amino acid position 59 to be replaced by a valine (V). 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	0.30
BayesDel_addAF	Benign	0.0068	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.042	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.013	D;D
Polyphen		0.96	P;.
Vest4		0.68
MutPred		0.71		Loss of catalytic residue at A59 (P = 0.0797);Loss of catalytic residue at A59 (P = 0.0797);
MVP		0.46
MPC		0.25
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.81
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1399134237; hg19: chr1-20442835;