22-38148291-A-G

Position:

• chr22-38148291-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003560.4(PLA2G6):​c.210-2638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 530,902 control chromosomes in the GnomAD database, including 39,957 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 0.40 (12542 hom., cov: 32)
  • Exomes 𝑓: 0.37 (27415 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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]

ENSG00000279080 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.210-2638T>C		intron_variant		ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.210-2638T>C		intron_variant		1	NM_003560.4	ENSP00000333142.3

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60647 AN: 151930 Hom.: 12520 Cov.: 32

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.374 AC: 141712 AN: 378854 Hom.: 27415 Cov.: 0 AF XY: 0.380 AC XY: 76622 AN XY: 201486

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.428

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.399 AC: 60727 AN: 152048 Hom.: 12542 Cov.: 32 AF XY: 0.402 AC XY: 29888 AN XY: 74328

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.381

Alfa AF: 0.363 Hom.: 17571

Bravo AF: 0.404

Asia WGS AF: 0.429 AC: 1496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.96
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2284063; hg19: chr22-38544298;