rs2016274700

Variant names:

• chr1-20086104-G-T
• rs2016274700
• NM_000929.3:c.62G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000929.3(PLA2G5):​c.62G>T​(p.Gly21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G21R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLA2G5 NM_000929.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.686
• Publications: 0 publications found

Genes affected

PLA2G5 (HGNC:9038): (phospholipase A2 group V) This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

PLA2G5 Gene-Disease associations (from GenCC):

• familial benign flecked retina

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet
• late-adult onset retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000929.3. 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
	PLA2G5	NM_000929.3	MANE Select	c.62G>T	p.Gly21Val	missense	Exon 3 of 5	NP_000920.1	P39877

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G5	ENST00000375108.4	TSL:1 MANE Select	c.62G>T	p.Gly21Val	missense	Exon 3 of 5	ENSP00000364249.3	P39877
	PLA2G5	ENST00000894073.1		c.62G>T	p.Gly21Val	missense	Exon 5 of 7	ENSP00000564132.1
	PLA2G5	ENST00000894074.1		c.62G>T	p.Gly21Val	missense	Exon 7 of 9	ENSP00000564133.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	0.11
Eigen_PC	Benign	0.032
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		0.69
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.16
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.010	D
Polyphen		0.78	P
Vest4		0.38
MutPred		0.69		Gain of methylation at K26 (P = 0.1245)
MVP		0.52
MPC		0.78
ClinPred		0.85	D
GERP RS		2.3
Varity_R		0.39
gMVP		0.79
Mutation Taster		=85/15	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: rs2016274700; hg19: chr1-20412597;