1-20115561-T-C

Variant names:

• chr1-20115561-T-C
• rs584367
• NM_012400.4:c.238A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012400.4(PLA2G2D):​c.238A>G​(p.Ser80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,609,566 control chromosomes in the GnomAD database, including 314,790 homozygotes. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.70 (38657 hom., cov: 31)
  • Exomes 𝑓: 0.61 (276133 hom.)
• Consequence: PLA2G2D NM_012400.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4482092E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G2D	NM_012400.4	c.238A>G	p.Ser80Gly	missense_variant	Exon 3 of 4	ENST00000375105.8	NP_036532.1
PLA2G2D	NM_001271814.2	c.185+772A>G		intron_variant	Intron 2 of 2		NP_001258743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G2D	ENST00000375105.8	c.238A>G	p.Ser80Gly	missense_variant	Exon 3 of 4	1	NM_012400.4	ENSP00000364246.3
PLA2G2D	ENST00000617227.1	c.185+772A>G		intron_variant	Intron 2 of 2	1		ENSP00000482871.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106121 AN: 151904 Hom.: 38605 Cov.: 31

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.693

GnomAD3 exomes AF: 0.658 AC: 165453 AN: 251336 Hom.: 55749 AF XY: 0.656 AC XY: 89053 AN XY: 135838

Gnomad AFR exome AF: 0.918

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.597

Gnomad EAS exome AF: 0.775

Gnomad SAS exome AF: 0.758

Gnomad FIN exome AF: 0.593

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.647

GnomAD4 exome AF: 0.610 AC: 889295 AN: 1457544 Hom.: 276133 Cov.: 37 AF XY: 0.613 AC XY: 444864 AN XY: 725386

Gnomad4 AFR exome AF: 0.927

Gnomad4 AMR exome AF: 0.685

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.730

Gnomad4 SAS exome AF: 0.760

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.581

Gnomad4 OTH exome AF: 0.639

GnomAD4 genome AF: 0.699 AC: 106226 AN: 152022 Hom.: 38657 Cov.: 31 AF XY: 0.701 AC XY: 52049 AN XY: 74298

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.687

Alfa AF: 0.614 Hom.: 61160

Bravo AF: 0.716

TwinsUK AF: 0.578 AC: 2144

ALSPAC AF: 0.581 AC: 2239

ESP6500AA AF: 0.903 AC: 3979

ESP6500EA AF: 0.582 AC: 5007

ExAC AF: 0.660 AC: 80197

Asia WGS AF: 0.719 AC: 2500 AN: 3478

EpiCase AF: 0.586

EpiControl AF: 0.595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.32
DANN	Benign	0.46
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.10	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.011
Sift	Benign	0.86	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.034
ClinPred		0.00041	T
GERP RS		-4.4
Varity_R		0.023
gMVP		0.18

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

Other links and lift over

dbSNP: rs584367; hg19: chr1-20442054; COSMIC: COSV64281827;