rs2284060

Variant names:

• chr22-38147446-T-C
• rs2284060
• NM_003560.4:c.210-1793A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003560.4(PLA2G6):​c.210-1793A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 168,824 control chromosomes in the GnomAD database, including 15,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (13782 hom., cov: 30)
  • Exomes 𝑓: 0.43 (1655 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 24 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

ENSG00000279080 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-38147446-T-C is Benign according to our data. Variant chr22-38147446-T-C is described in ClinVar as Benign. ClinVar VariationId is 3255255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.210-1793A>G		intron_variant	Intron 2 of 16	ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.210-1793A>G		intron_variant	Intron 2 of 16	1	NM_003560.4	ENSP00000333142.3

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63907 AN: 151628 Hom.: 13771 Cov.: 30

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.425

GnomAD4 exome AF: 0.433 AC: 7394 AN: 17078 Hom.: 1655 Cov.: 0 AF XY: 0.435 AC XY: 3546 AN XY: 8158

African (AFR) AF: 0.359 AC: 28 AN: 78

American (AMR) AF: 0.500 AC: 6 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AF: 0.500 AC: 47 AN: 94

European-Finnish (FIN) AF: 0.428 AC: 6285 AN: 14700

Middle Eastern (MID) AF: 0.473 AC: 773 AN: 1634

European-Non Finnish (NFE) AF: 0.433 AC: 117 AN: 270

Other (OTH) AF: 0.479 AC: 135 AN: 282

GnomAD4 genome AF: 0.422 AC: 63971 AN: 151746 Hom.: 13782 Cov.: 30 AF XY: 0.424 AC XY: 31454 AN XY: 74118

African (AFR) AF: 0.381 AC: 15736 AN: 41354

American (AMR) AF: 0.454 AC: 6911 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1703 AN: 3460

East Asian (EAS) AF: 0.326 AC: 1688 AN: 5170

South Asian (SAS) AF: 0.545 AC: 2621 AN: 4806

European-Finnish (FIN) AF: 0.416 AC: 4379 AN: 10514

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

European-Non Finnish (NFE) AF: 0.434 AC: 29454 AN: 67920

Other (OTH) AF: 0.428 AC: 901 AN: 2104

Alfa AF: 0.433 Hom.: 35399

Bravo AF: 0.416

Asia WGS AF: 0.469 AC: 1634 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 63% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 59. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.49
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs2284060; hg19: chr22-38543453; COSMIC: COSV59267816; COSMIC: COSV59267816;