22-38186490-G-A

Variant summary

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

The ENST00000660610.1(PLA2G6):​c.-41-17023C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,698 control chromosomes in the GnomAD database, including 19,958 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 0.50 ( 19958 hom., cov: 30)

Consequence

PLA2G6
ENST00000660610.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.350

Publications

6 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

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=-0.78).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLA2G6ENST00000660610.1 linkc.-41-17023C>T intron_variant Intron 1 of 16 ENSP00000499555.1 O60733-1
PLA2G6ENST00000594306.1 linkc.-45-17019C>T intron_variant Intron 1 of 1 4 ENSP00000473160.1 M0R3D9
PLA2G6ENST00000417303.6 linkn.68+5543C>T intron_variant Intron 1 of 3 4

Frequencies

GnomAD3 genomes
AF:
0.504
AC:
76358
AN:
151580
Hom.:
19967
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.382
Gnomad AMI
AF:
0.355
Gnomad AMR
AF:
0.503
Gnomad ASJ
AF:
0.531
Gnomad EAS
AF:
0.600
Gnomad SAS
AF:
0.370
Gnomad FIN
AF:
0.601
Gnomad MID
AF:
0.404
Gnomad NFE
AF:
0.565
Gnomad OTH
AF:
0.528
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.503
AC:
76364
AN:
151698
Hom.:
19958
Cov.:
30
AF XY:
0.502
AC XY:
37168
AN XY:
74104
show subpopulations
African (AFR)
AF:
0.381
AC:
15765
AN:
41360
American (AMR)
AF:
0.503
AC:
7648
AN:
15190
Ashkenazi Jewish (ASJ)
AF:
0.531
AC:
1844
AN:
3470
East Asian (EAS)
AF:
0.600
AC:
3087
AN:
5142
South Asian (SAS)
AF:
0.369
AC:
1779
AN:
4816
European-Finnish (FIN)
AF:
0.601
AC:
6318
AN:
10516
Middle Eastern (MID)
AF:
0.404
AC:
118
AN:
292
European-Non Finnish (NFE)
AF:
0.565
AC:
38380
AN:
67896
Other (OTH)
AF:
0.523
AC:
1103
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1830
3660
5489
7319
9149
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
672
1344
2016
2688
3360
<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:
0.534
Hom.:
2769
Bravo
AF:
0.496
Asia WGS
AF:
0.457
AC:
1585
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
4.0
DANN
Benign
0.89
PhyloP100
-0.35
Mutation Taster
=100/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs5750558; hg19: chr22-38582497; API