1-20115561-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 51 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012400.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2D	NM_012400.4	MANE Select	c.238A>G	p.Ser80Gly	missense	Exon 3 of 4	NP_036532.1	Q9UNK4-1
	PLA2G2D	NM_001271814.2		c.185+772A>G		intron	N/A	NP_001258743.1	Q9UNK4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2D	ENST00000375105.8	TSL:1 MANE Select	c.238A>G	p.Ser80Gly	missense	Exon 3 of 4	ENSP00000364246.3	Q9UNK4-1
	PLA2G2D	ENST00000617227.1	TSL:1	c.185+772A>G		intron	N/A	ENSP00000482871.1	Q9UNK4-2

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

GnomAD2 exomes AF: 0.658 AC: 165453 AN: 251336 AF XY: 0.656

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 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

African (AFR) AF: 0.927 AC: 31002 AN: 33436

American (AMR) AF: 0.685 AC: 30628 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 15482 AN: 26118

East Asian (EAS) AF: 0.730 AC: 28976 AN: 39688

South Asian (SAS) AF: 0.760 AC: 65508 AN: 86180

European-Finnish (FIN) AF: 0.591 AC: 31557 AN: 53410

Middle Eastern (MID) AF: 0.746 AC: 4298 AN: 5760

European-Non Finnish (NFE) AF: 0.581 AC: 643383 AN: 1108008

Other (OTH) AF: 0.639 AC: 38461 AN: 60224

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

African (AFR) AF: 0.916 AC: 37982 AN: 41482

American (AMR) AF: 0.689 AC: 10525 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2056 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3893 AN: 5156

South Asian (SAS) AF: 0.737 AC: 3553 AN: 4820

European-Finnish (FIN) AF: 0.592 AC: 6249 AN: 10550

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.584 AC: 39672 AN: 67942

Other (OTH) AF: 0.687 AC: 1452 AN: 2114

Alfa AF: 0.632 Hom.: 91999

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 v4.9

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	0.0000015	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.10	N
PhyloP100		-1.3
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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