1-20115561-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012400.4(PLA2G2D):​c.238A>C​(p.Ser80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)
• Consequence: PLA2G2D NM_012400.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 50 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038411587).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2D	NM_012400.4	MANE Select	c.238A>C	p.Ser80Arg	missense	Exon 3 of 4	NP_036532.1
	PLA2G2D	NM_001271814.2		c.185+772A>C		intron	N/A	NP_001258743.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G2D	ENST00000375105.8	TSL:1 MANE Select	c.238A>C	p.Ser80Arg	missense	Exon 3 of 4	ENSP00000364246.3
	PLA2G2D	ENST00000617227.1	TSL:1	c.185+772A>C		intron	N/A	ENSP00000482871.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.043
DANN	Benign	0.49
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-1.3
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.016
Sift	Benign	0.67	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.42		Loss of ubiquitination at K83 (P = 0.0471)
MVP		0.099
MPC		0.039
ClinPred		0.043	T
GERP RS		-4.4
Varity_R		0.065
gMVP		0.16
Mutation Taster		=100/0	polymorphism

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;