rs2413502

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003560.4(PLA2G6):c.1086C>T(p.Asn362Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,612,058 control chromosomes in the GnomAD database, including 1,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 785 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 674 hom. )

Consequence

PLA2G6
NM_003560.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0780

Variant links:

Genes affected

PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]

PLA2G6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 22-38129554-G-A is Benign according to our data. Variant chr22-38129554-G-A is described in ClinVar as [Benign]. Clinvar id is 159727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-38129554-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.078 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G6	NM_003560.4 link	c.1086C>T	p.Asn362Asn	synonymous_variant	Exon 8 of 17	ENST00000332509.8	NP_003551.2	O60733-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8 link	c.1086C>T	p.Asn362Asn	synonymous_variant	Exon 8 of 17	1	NM_003560.4	ENSP00000333142.3		O60733-1

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8347

AN:

152126

Hom.:

783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0239

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0150

AC:

3763

AN:

251416

Hom.:

320

AF XY:

0.0111

AC XY:

1513

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00634

AC:

9258

AN:

1459814

Hom.:

674

Cov.:

AF XY:

0.00561

AC XY:

4077

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.192

Gnomad4 AMR exome

AF:

0.0123

Gnomad4 ASJ exome

AF:

0.00322

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000534

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00111

Gnomad4 OTH exome

AF:

0.0137

GnomAD4 genome

AF:

0.0550

AC:

8371

AN:

152244

Hom.:

785

Cov.:

AF XY:

0.0533

AC XY:

3967

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.0239

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0118

Hom.:

258

Bravo

AF:

0.0618

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Infantile neuroaxonal dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PLA2G6-associated neurodegeneration

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.8

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over