22-38167464-C-T

Variant names:

• chr22-38167464-C-T
• rs132985
• NM_003560.4:c.209+1754G>A

Variant summary

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

The NM_003560.4(PLA2G6):​c.209+1754G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,772 control chromosomes in the GnomAD database, including 20,224 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 (20224 hom., cov: 31)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 48 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003560.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G6	NM_003560.4	MANE Select	c.209+1754G>A		intron	N/A	NP_003551.2
	PLA2G6	NM_001349864.2		c.209+1754G>A		intron	N/A	NP_001336793.1
	PLA2G6	NM_001004426.3		c.209+1754G>A		intron	N/A	NP_001004426.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G6	ENST00000332509.8	TSL:1 MANE Select	c.209+1754G>A		intron	N/A	ENSP00000333142.3
	PLA2G6	ENST00000402064.5	TSL:1	c.209+1754G>A		intron	N/A	ENSP00000386100.1
	PLA2G6	ENST00000668949.1		c.209+1754G>A		intron	N/A	ENSP00000499711.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77107 AN: 151654 Hom.: 20193 Cov.: 31

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.509 AC: 77204 AN: 151772 Hom.: 20224 Cov.: 31 AF XY: 0.509 AC XY: 37728 AN XY: 74168

African (AFR) AF: 0.605 AC: 25005 AN: 41350

American (AMR) AF: 0.511 AC: 7786 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1653 AN: 3464

East Asian (EAS) AF: 0.395 AC: 2026 AN: 5128

South Asian (SAS) AF: 0.635 AC: 3060 AN: 4820

European-Finnish (FIN) AF: 0.408 AC: 4296 AN: 10522

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31616 AN: 67926

Other (OTH) AF: 0.493 AC: 1040 AN: 2110

Alfa AF: 0.486 Hom.: 56599

Bravo AF: 0.516

Asia WGS AF: 0.551 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs132985; hg19: chr22-38563471;