chr22-38198661-G-A

Variant names:

• chr22-38198661-G-A
• rs2899297
• ENST00000660610.1:c.-42+15792C>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+6632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,878 control chromosomes in the GnomAD database, including 22,060 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 0.53 (22060 hom., cov: 31)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 9 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

ENSG00000298301 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 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.-42+15792C>T		intron_variant	Intron 1 of 16			ENSP00000499555.1
PLA2G6	ENST00000594306.1	c.-46+6632C>T		intron_variant	Intron 1 of 1	4		ENSP00000473160.1
ENSG00000298301	ENST00000754572.1	n.185-3784C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80066 AN: 151760 Hom.: 22074 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.527 AC: 80084 AN: 151878 Hom.: 22060 Cov.: 31 AF XY: 0.526 AC XY: 39069 AN XY: 74214

African (AFR) AF: 0.369 AC: 15283 AN: 41394

American (AMR) AF: 0.518 AC: 7887 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2068 AN: 3472

East Asian (EAS) AF: 0.740 AC: 3823 AN: 5166

South Asian (SAS) AF: 0.458 AC: 2209 AN: 4820

European-Finnish (FIN) AF: 0.613 AC: 6459 AN: 10544

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40703 AN: 67932

Other (OTH) AF: 0.541 AC: 1141 AN: 2110

Alfa AF: 0.561 Hom.: 10296

Bravo AF: 0.519

Asia WGS AF: 0.553 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.63
PhyloP100		-0.99

Splicing

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

Other links and lift over

dbSNP: rs2899297; hg19: chr22-38594668;