chr22-38200093-G-A

Variant names:

• chr22-38200093-G-A
• rs9607517
• ENST00000660610.1:c.-42+14360C>T

Variant summary

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

The ENST00000594306.1(PLA2G6):​c.-46+5200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,044 control chromosomes in the GnomAD database, including 18,337 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 0.47 (18337 hom., cov: 32)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 2 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• neurodegeneration with brain iron accumulation 2B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• PLA2G6-associated neurodegeneration

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive Parkinson disease 14

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics

ENSG00000298301 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 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.-42+14360C>T		intron	N/A	ENSP00000499555.1	O60733-1
	PLA2G6	ENST00000594306.1	TSL:4	c.-46+5200C>T		intron	N/A	ENSP00000473160.1	M0R3D9
	ENSG00000298301	ENST00000754572.1		n.184+3193C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71409 AN: 151926 Hom.: 18348 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.470 AC: 71417 AN: 152044 Hom.: 18337 Cov.: 32 AF XY: 0.470 AC XY: 34958 AN XY: 74328

African (AFR) AF: 0.262 AC: 10856 AN: 41472

American (AMR) AF: 0.489 AC: 7466 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3103 AN: 5178

South Asian (SAS) AF: 0.385 AC: 1859 AN: 4828

European-Finnish (FIN) AF: 0.601 AC: 6336 AN: 10542

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38426 AN: 67984

Other (OTH) AF: 0.487 AC: 1026 AN: 2106

Alfa AF: 0.503 Hom.: 2655

Bravo AF: 0.457

Asia WGS AF: 0.455 AC: 1578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.70
PhyloP100		-0.20

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9607517;

hg19: chr22-38596100;