rs2267369

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003560.4(PLA2G6):c.87G>A(p.Val29Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 1,614,072 control chromosomes in the GnomAD database, including 2,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 842 hom., cov: 32)

Exomes 𝑓: 0.028 ( 1433 hom. )

Consequence

PLA2G6
NM_003560.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.611

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

neurodegeneration with brain iron accumulation 2A
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
neurodegeneration with brain iron accumulation 2B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
PLA2G6-associated neurodegeneration
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive Parkinson disease 14
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

PLA2G6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 22-38169340-C-T is Benign according to our data. Variant chr22-38169340-C-T is described in ClinVar as Benign. ClinVar VariationId is 159781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.611 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G6	NM_003560.4 link	c.87G>A	p.Val29Val	synonymous_variant	Exon 2 of 17	ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8 link	c.87G>A	p.Val29Val	synonymous_variant	Exon 2 of 17	1	NM_003560.4	ENSP00000333142.3

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10617

AN:

152130

Hom.:

839

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.0364

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0605

Gnomad FIN

AF:

0.00669

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0489

GnomAD2 exomes

AF:

0.0406

AC:

10212

AN:

251232

AF XY:

0.0384

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.00869

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0277

AC:

40560

AN:

1461824

Hom.:

1433

Cov.:

AF XY:

0.0280

AC XY:

20391

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.191

AC:

6379

AN:

33474

American (AMR)

AF:

0.0193

AC:

864

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

437

AN:

26136

East Asian (EAS)

AF:

0.116

AC:

4619

AN:

39696

South Asian (SAS)

AF:

0.0625

AC:

5394

AN:

86246

European-Finnish (FIN)

AF:

0.00884

AC:

472

AN:

53418

Middle Eastern (MID)

AF:

0.0283

AC:

163

AN:

5768

European-Non Finnish (NFE)

AF:

0.0179

AC:

19864

AN:

1111974

Other (OTH)

AF:

0.0392

AC:

2368

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2350

4700

7049

9399

11749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

968

1936

2904

3872

4840

<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:

0.0699

AC:

10644

AN:

152248

Hom.:

842

Cov.:

AF XY:

0.0695

AC XY:

5173

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.187

AC:

7758

AN:

41530

American (AMR)

AF:

0.0363

AC:

556

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.116

AC:

598

AN:

5168

South Asian (SAS)

AF:

0.0617

AC:

298

AN:

4826

European-Finnish (FIN)

AF:

0.00669

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0514

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0166

AC:

1129

AN:

68026

Other (OTH)

AF:

0.0498

AC:

105

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

452

905

1357

1810

2262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0343

Hom.:

1030

Bravo

AF:

0.0760

Asia WGS

AF:

0.0870

AC:

302

AN:

3478

EpiCase

AF:

0.0170

EpiControl

AF:

0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic 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

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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 13, 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

-0.73

CADD

Benign

7.5

(source)

DANN

Benign

0.57

PhyloP100

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over