rs2413507

Variant names:

• chr22-38197421-A-G
• rs2413507
• ENST00000660610.1:c.-42+17032T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-38197421-A-G
• chr22-38197421-A-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+7872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,636 control chromosomes in the GnomAD database, including 20,408 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 (20408 hom., cov: 30)
• Consequence: PLA2G6 ENST00000594306.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 3 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=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 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+17032T>C		intron	N/A	ENSP00000499555.1	O60733-1
	PLA2G6	ENST00000594306.1	TSL:4	c.-46+7872T>C		intron	N/A	ENSP00000473160.1	M0R3D9
	ENSG00000298301	ENST00000754572.1		n.185-2544T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77489 AN: 151522 Hom.: 20407 Cov.: 30

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.511 AC: 77526 AN: 151636 Hom.: 20408 Cov.: 30 AF XY: 0.511 AC XY: 37843 AN XY: 74086

African (AFR) AF: 0.406 AC: 16760 AN: 41298

American (AMR) AF: 0.506 AC: 7710 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1897 AN: 3472

East Asian (EAS) AF: 0.600 AC: 3087 AN: 5142

South Asian (SAS) AF: 0.385 AC: 1844 AN: 4790

European-Finnish (FIN) AF: 0.601 AC: 6306 AN: 10486

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.565 AC: 38411 AN: 67930

Other (OTH) AF: 0.511 AC: 1071 AN: 2094

Alfa AF: 0.529 Hom.: 2621

Bravo AF: 0.503

Asia WGS AF: 0.466 AC: 1616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.4
DANN	Benign	0.12
PhyloP100		-0.35

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: rs2413507;

hg19: chr22-38593428;