rs2267369

Positions:

chr22-38169340-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:

PLA2G6 (HGNC:):

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=-0.73).

BP6

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

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/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4 linkuse as main transcript	c.87G>A	p.Val29Val	synonymous_variant	2/17	ENST00000332509.8	NP_003551.2	O60733-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8 linkuse as main transcript	c.87G>A	p.Val29Val	synonymous_variant	2/17	1	NM_003560.4	ENSP00000333142.3		O60733-1

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

GnomAD3 exomes

AF:

0.0406

AC:

10212

AN:

251232

Hom.:

545

AF XY:

0.0384

AC XY:

5211

AN XY:

135798

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 SAS exome

AF:

0.0650

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

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0193

Gnomad4 ASJ exome

AF:

0.0167

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.0625

Gnomad4 FIN exome

AF:

0.00884

Gnomad4 NFE exome

AF:

0.0179

Gnomad4 OTH exome

AF:

0.0392

GnomAD4 genome

AF:

0.0699

AC:

10644

AN:

152248

Hom.:

842

Cov.:

AF XY:

0.0695

AC XY:

5173

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.187

Gnomad4 AMR

AF:

0.0363

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.0617

Gnomad4 FIN

AF:

0.00669

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0498

Alfa

AF:

0.0281

Hom.:

312

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

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Infantile neuroaxonal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

PLA2G6-associated neurodegeneration

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

DANN

Benign

0.57

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