22-38199253-A-T

Variant names:

• chr22-38199253-A-T
• rs5750561
• ENST00000660610.1:c.-42+15200T>A

Variant summary

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

The ENST00000594306.1(PLA2G6):​c.-46+6040T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,672 control chromosomes in the GnomAD database, including 21,827 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 0.52 (21827 hom., cov: 32)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.979
• Publications: 5 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)

ENSG00000298301 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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+15200T>A		intron	N/A	ENSP00000499555.1	O60733-1
	PLA2G6	ENST00000594306.1	TSL:4	c.-46+6040T>A		intron	N/A	ENSP00000473160.1	M0R3D9
	ENSG00000298301	ENST00000754572.1		n.184+4033T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79609 AN: 151556 Hom.: 21845 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.525 AC: 79620 AN: 151672 Hom.: 21827 Cov.: 32 AF XY: 0.524 AC XY: 38789 AN XY: 74082

African (AFR) AF: 0.365 AC: 15106 AN: 41396

American (AMR) AF: 0.515 AC: 7845 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2062 AN: 3466

East Asian (EAS) AF: 0.738 AC: 3783 AN: 5126

South Asian (SAS) AF: 0.458 AC: 2202 AN: 4812

European-Finnish (FIN) AF: 0.609 AC: 6392 AN: 10500

Middle Eastern (MID) AF: 0.483 AC: 140 AN: 290

European-Non Finnish (NFE) AF: 0.598 AC: 40583 AN: 67836

Other (OTH) AF: 0.540 AC: 1136 AN: 2104

Alfa AF: 0.557 Hom.: 3019

Bravo AF: 0.518

Asia WGS AF: 0.553 AC: 1918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.67
PhyloP100		0.98

Splicing

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

Other links and lift over

dbSNP: rs5750561; hg19: chr22-38595260;