rs5750547

Variant names:

• chr22-38150693-G-A
• rs5750547
• NM_003560.4:c.210-5040C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-38150693-G-A
• chr22-38150693-G-C
• chr22-38150693-G-T

Variant summary

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

The NM_003560.4(PLA2G6):​c.210-5040C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,128 control chromosomes in the GnomAD database, including 11,494 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 0.38 (11494 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.210-5040C>T		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.210-5040C>T		intron_variant	Intron 2 of 16	1	NM_003560.4	ENSP00000333142.3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58325 AN: 152006 Hom.: 11470 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

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) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.384 AC: 58401 AN: 152124 Hom.: 11494 Cov.: 33 AF XY: 0.387 AC XY: 28806 AN XY: 74364

African (AFR) AF: 0.434 AC: 18010 AN: 41498

American (AMR) AF: 0.421 AC: 6432 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1230 AN: 3472

East Asian (EAS) AF: 0.258 AC: 1334 AN: 5176

South Asian (SAS) AF: 0.481 AC: 2323 AN: 4830

European-Finnish (FIN) AF: 0.342 AC: 3608 AN: 10558

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.355 AC: 24107 AN: 67994

Other (OTH) AF: 0.373 AC: 786 AN: 2110

Alfa AF: 0.364 Hom.: 11296

Bravo AF: 0.387

Asia WGS AF: 0.423 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.19
PhyloP100		-1.7
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: rs5750547; hg19: chr22-38546700;