Genetic Variant PLA2G5:n.497+62G>A (chr1-20069094-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000460175.5(PLA2G5):n.497+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 467,400 control chromosomes in the GnomAD database, including 2,092 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.062 ( 488 hom., cov: 32)

Exomes 𝑓: 0.085 ( 1604 hom. )

Consequence

PLA2G5
ENST00000460175.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.931

Publications

7 publications found

Variant links:

COSMIC-nc: COSV64282876

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: G2P, Ambry Genetics, Orphanet
late-adult onset retinitis pigmentosa
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

PLA2G5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
PLA2G5	XM_005245891.6 link	c.83+62G>A	intron_variant	Intron 4 of 7	XP_005245948.1
PLA2G5	XM_005245892.6 link	c.83+62G>A	intron_variant	Intron 3 of 6	XP_005245949.1
PLA2G5	XM_011541586.4 link	c.83+62G>A	intron_variant	Intron 2 of 5	XP_011539888.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
PLA2G5	ENST00000460175.5 link	n.497+62G>A	intron_variant	Intron 3 of 6	3
PLA2G5	ENST00000465698.5 link	n.501+62G>A	intron_variant	Intron 3 of 7	3
PLA2G5	ENST00000469069.5 link	n.524+62G>A	intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.0625

AC:

9512

AN:

152084

Hom.:

491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.0659

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0539

Gnomad OTH

AF:

0.0578

GnomAD4 exome

AF:

0.0850

AC:

26799

AN:

315198

Hom.:

1604

AF XY:

0.0889

AC XY:

15870

AN XY:

178462

show subpopulations

African (AFR)

AF:

0.0181

AC:

160

AN:

8838

American (AMR)

AF:

0.135

AC:

3649

AN:

27008

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

1229

AN:

10746

East Asian (EAS)

AF:

0.261

AC:

2395

AN:

9180

South Asian (SAS)

AF:

0.127

AC:

7543

AN:

59420

European-Finnish (FIN)

AF:

0.0594

AC:

758

AN:

12760

Middle Eastern (MID)

AF:

0.164

AC:

461

AN:

2804

European-Non Finnish (NFE)

AF:

0.0556

AC:

9437

AN:

169850

Other (OTH)

AF:

0.0800

AC:

1167

AN:

14592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1153

2305

3458

4610

5763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0624

AC:

9500

AN:

152202

Hom.:

488

Cov.:

AF XY:

0.0673

AC XY:

5007

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0216

AC:

896

AN:

41550

American (AMR)

AF:

0.110

AC:

1683

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

429

AN:

3468

East Asian (EAS)

AF:

0.254

AC:

1311

AN:

5160

South Asian (SAS)

AF:

0.132

AC:

638

AN:

4824

European-Finnish (FIN)

AF:

0.0659

AC:

698

AN:

10594

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0539

AC:

3665

AN:

68018

Other (OTH)

AF:

0.0568

AC:

120

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

455

911

1366

1822

2277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0519

Hom.:

139

Bravo

AF:

0.0632

Asia WGS

AF:

0.167

AC:

581

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.80

(source)

DANN

Benign

0.42

PhyloP100

-0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over