Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000332509.8(PLA2G6):c.957G>A(p.Thr319Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,563,298 control chromosomes in the GnomAD database, including 1,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 774 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 637 hom. )

Consequence

PLA2G6
ENST00000332509.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.85

Publications

7 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:

ENSG00000279080 (HGNC:):

ENSG00000279080 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.068).

BP6

Variant 22-38132951-C-T is Benign according to our data. Variant chr22-38132951-C-T is described in ClinVar as Benign. ClinVar VariationId is 159782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000332509.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLA2G6	NM_003560.4	MANE Select	c.957G>A	p.Thr319Thr	synonymous	Exon 7 of 17	NP_003551.2
PLA2G6	NM_001349864.2		c.957G>A	p.Thr319Thr	synonymous	Exon 7 of 17	NP_001336793.1
PLA2G6	NM_001004426.3		c.957G>A	p.Thr319Thr	synonymous	Exon 7 of 16	NP_001004426.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLA2G6	ENST00000332509.8	TSL:1 MANE Select	c.957G>A	p.Thr319Thr	synonymous	Exon 7 of 17	ENSP00000333142.3
PLA2G6	ENST00000402064.5	TSL:1	c.957G>A	p.Thr319Thr	synonymous	Exon 7 of 16	ENSP00000386100.1
PLA2G6	ENST00000668949.1		c.957G>A	p.Thr319Thr	synonymous	Exon 7 of 17	ENSP00000499711.1

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8324

AN:

152164

Hom.:

772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.0358

GnomAD2 exomes

AF:

0.0139

AC:

2403

AN:

173402

AF XY:

0.0105

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00332

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00196

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.00659

AC:

9298

AN:

1411016

Hom.:

637

Cov.:

AF XY:

0.00592

AC XY:

4128

AN XY:

697316

show subpopulations

African (AFR)

AF:

0.191

AC:

6151

AN:

32236

American (AMR)

AF:

0.0126

AC:

471

AN:

37322

Ashkenazi Jewish (ASJ)

AF:

0.00328

AC:

AN:

25292

East Asian (EAS)

AF:

0.0000543

AC:

AN:

36824

South Asian (SAS)

AF:

0.000637

AC:

AN:

80074

European-Finnish (FIN)

AF:

0.0000821

AC:

AN:

48718

Middle Eastern (MID)

AF:

0.0189

AC:

108

AN:

5706

European-Non Finnish (NFE)

AF:

0.00148

AC:

1611

AN:

1086334

Other (OTH)

AF:

0.0140

AC:

817

AN:

58510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

503

1006

1509

2012

2515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<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:

0.0548

AC:

8348

AN:

152282

Hom.:

774

Cov.:

AF XY:

0.0532

AC XY:

3962

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.187

AC:

7772

AN:

41548

American (AMR)

AF:

0.0236

AC:

361

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00169

AC:

115

AN:

68014

Other (OTH)

AF:

0.0354

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

350

699

1049

1398

1748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0312

Hom.:

198

Bravo

AF:

0.0615

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Infantile neuroaxonal dystrophy (1)

PLA2G6-associated neurodegeneration (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.017

(source)

DANN

Benign

0.73

PhyloP100

-1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over