chr22-38150026-T-C

Variant names:

• chr22-38150026-T-C
• rs5756931
• NM_003560.4:c.210-4373A>G

Variant summary

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

The NM_003560.4(PLA2G6):​c.210-4373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 131,610 control chromosomes in the GnomAD database, including 8,087 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 0.33 (8087 hom., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 73 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003560.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G6	NM_003560.4	MANE Select	c.210-4373A>G		intron	N/A	NP_003551.2
	PLA2G6	NM_001349864.2		c.210-4373A>G		intron	N/A	NP_001336793.1
	PLA2G6	NM_001004426.3		c.210-4373A>G		intron	N/A	NP_001004426.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G6	ENST00000332509.8	TSL:1 MANE Select	c.210-4373A>G		intron	N/A	ENSP00000333142.3
	PLA2G6	ENST00000402064.5	TSL:1	c.210-4373A>G		intron	N/A	ENSP00000386100.1
	ENSG00000279080	ENST00000624072.1	TSL:6	n.19811T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 43216 AN: 131564 Hom.: 8081 Cov.: 22

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.476

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.367

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.328 AC: 43232 AN: 131610 Hom.: 8087 Cov.: 22 AF XY: 0.333 AC XY: 21039 AN XY: 63150

African (AFR) AF: 0.125 AC: 4141 AN: 33204

American (AMR) AF: 0.420 AC: 5417 AN: 12912

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1444 AN: 3298

East Asian (EAS) AF: 0.137 AC: 586 AN: 4264

South Asian (SAS) AF: 0.479 AC: 2009 AN: 4192

European-Finnish (FIN) AF: 0.413 AC: 3055 AN: 7398

Middle Eastern (MID) AF: 0.483 AC: 114 AN: 236

European-Non Finnish (NFE) AF: 0.401 AC: 25431 AN: 63470

Other (OTH) AF: 0.370 AC: 657 AN: 1778

Alfa AF: 0.360 Hom.: 19115

Bravo AF: 0.295

Asia WGS AF: 0.297 AC: 976 AN: 3286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.85
PhyloP100		0.41
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: rs5756931; hg19: chr22-38546033;