dbSNP rs738322: PLA2G6:c.-45-3528T>C (chr22-38172999-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003560.4(PLA2G6):c.-45-3528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,098 control chromosomes in the GnomAD database, including 20,757 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 0.51 ( 20757 hom., cov: 32)

Consequence

PLA2G6
NM_003560.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.249

Publications

46 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G6	NM_003560.4 link	c.-45-3528T>C		intron_variant	Intron 1 of 16	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.-45-3528T>C		intron_variant	Intron 1 of 16	1	NM_003560.4	ENSP00000333142.3		O60733-1

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78200

AN:

151980

Hom.:

20723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.480

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.470

Gnomad OTH

AF:

0.493

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.515

AC:

78300

AN:

152098

Hom.:

20757

Cov.:

AF XY:

0.514

AC XY:

38236

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.615

AC:

25516

AN:

41494

American (AMR)

AF:

0.513

AC:

7844

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.480

AC:

1668

AN:

3472

East Asian (EAS)

AF:

0.400

AC:

2070

AN:

5170

South Asian (SAS)

AF:

0.637

AC:

3074

AN:

4824

European-Finnish (FIN)

AF:

0.411

AC:

4347

AN:

10578

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.470

AC:

31963

AN:

67958

Other (OTH)

AF:

0.499

AC:

1054

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1963

3926

5890

7853

9816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.488

Hom.:

49031

Bravo

AF:

0.522

Asia WGS

AF:

0.551

AC:

1920

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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rs738322

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over