ENST00000660610.1:c.-41-17023C>T

Variant names:

• chr22-38186490-G-A
• rs5750558
• ENST00000660610.1:c.-41-17023C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 6 publications found

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

ACMG classification

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
PLA2G6	ENST00000660610.1	c.-41-17023C>T		intron_variant	Intron 1 of 16			ENSP00000499555.1
PLA2G6	ENST00000594306.1	c.-45-17019C>T		intron_variant	Intron 1 of 1	4		ENSP00000473160.1
PLA2G6	ENST00000417303.6	n.68+5543C>T		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76358 AN: 151580 Hom.: 19967 Cov.: 30

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

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

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

Other links and lift over

dbSNP: rs5750558; hg19: chr22-38582497;