chr22-38184910-G-T

Variant names:

• chr22-38184910-G-T
• rs13056506
• ENST00000660610.1:c.-41-15443C>A

Variant summary

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

The ENST00000594306.1(PLA2G6):​c.-45-15439C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,024 control chromosomes in the GnomAD database, including 23,902 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 0.56 (23902 hom., cov: 32)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.309
• 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• 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: Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594306.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G6	ENST00000660610.1		c.-41-15443C>A		intron	N/A	ENSP00000499555.1	O60733-1
	PLA2G6	ENST00000885143.1		c.-46+7123C>A		intron	N/A	ENSP00000555202.1
	PLA2G6	ENST00000955628.1		c.-46+7123C>A		intron	N/A	ENSP00000625687.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84426 AN: 151906 Hom.: 23915 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.555 AC: 84432 AN: 152024 Hom.: 23902 Cov.: 32 AF XY: 0.552 AC XY: 41032 AN XY: 74298

African (AFR) AF: 0.472 AC: 19545 AN: 41438

American (AMR) AF: 0.529 AC: 8071 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2013 AN: 3466

East Asian (EAS) AF: 0.720 AC: 3725 AN: 5174

South Asian (SAS) AF: 0.450 AC: 2171 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6477 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40710 AN: 67970

Other (OTH) AF: 0.573 AC: 1212 AN: 2116

Alfa AF: 0.561 Hom.: 16324

Bravo AF: 0.551

Asia WGS AF: 0.542 AC: 1883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.73
DANN	Benign	0.67
PhyloP100		0.31
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: rs13056506; hg19: chr22-38580917;