rs2016755

Variant names:

• chr22-38143597-A-G
• rs2016755
• NM_003560.4:c.426-309T>C

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.426-309T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 482,158 control chromosomes in the GnomAD database, including 53,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18597 hom., cov: 32)
  • Exomes 𝑓: 0.45 (34697 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70
• Publications: 11 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=-0.86).
• BP6: Variant 22-38143597-A-G is Benign according to our data. Variant chr22-38143597-A-G is described in ClinVar as Benign. ClinVar VariationId is 1220853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.426-309T>C		intron_variant	Intron 3 of 16	ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.426-309T>C		intron_variant	Intron 3 of 16	1	NM_003560.4	ENSP00000333142.3

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73585 AN: 151914 Hom.: 18581 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.452 AC: 149114 AN: 330126 Hom.: 34697 Cov.: 0 AF XY: 0.459 AC XY: 81032 AN XY: 176378

African (AFR) AF: 0.613 AC: 5889 AN: 9600

American (AMR) AF: 0.487 AC: 7551 AN: 15516

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 4506 AN: 9748

East Asian (EAS) AF: 0.275 AC: 5236 AN: 19014

South Asian (SAS) AF: 0.553 AC: 24993 AN: 45222

European-Finnish (FIN) AF: 0.398 AC: 7107 AN: 17860

Middle Eastern (MID) AF: 0.529 AC: 725 AN: 1370

European-Non Finnish (NFE) AF: 0.438 AC: 84643 AN: 193342

Other (OTH) AF: 0.459 AC: 8464 AN: 18454

GnomAD4 genome AF: 0.484 AC: 73656 AN: 152032 Hom.: 18597 Cov.: 32 AF XY: 0.484 AC XY: 35934 AN XY: 74304

African (AFR) AF: 0.606 AC: 25137 AN: 41454

American (AMR) AF: 0.489 AC: 7473 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1614 AN: 3464

East Asian (EAS) AF: 0.289 AC: 1491 AN: 5166

South Asian (SAS) AF: 0.565 AC: 2724 AN: 4824

European-Finnish (FIN) AF: 0.387 AC: 4082 AN: 10558

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29464 AN: 67982

Other (OTH) AF: 0.477 AC: 1005 AN: 2108

Alfa AF: 0.449 Hom.: 30774

Bravo AF: 0.494

Asia WGS AF: 0.480 AC: 1674 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.43
PhyloP100		-1.7
PromoterAI		-0.073	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2016755; hg19: chr22-38539604;