22-38140854-C-G

Variant summary

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

The NM_003560.4(PLA2G6):c.610-685G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,478 control chromosomes in the GnomAD database, including 31,111 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 0.62 (31015 hom., cov: 31)
  • Exomes 𝑓: 0.57 (96 hom.)
• Consequence: PLA2G6 NM_003560.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G6	NM_003560.4	c.610-685G>C		intron_variant		ENST00000332509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000332509.8	c.610-685G>C		intron_variant		1	NM_003560.4	P3
	ENST00000624072.1	n.10639C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94547 AN: 151854 Hom.: 30966 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.567 AC: 287 AN: 506 Hom.: 96 Cov.: 0 AF XY: 0.596 AC XY: 162 AN XY: 272

Gnomad4 AMR exome AF: 0.617

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.551

Gnomad4 OTH exome AF: 0.864

GnomAD4 genome AF: 0.623 AC: 94656 AN: 151972 Hom.: 31015 Cov.: 31 AF XY: 0.623 AC XY: 46282 AN XY: 74252

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.613

Alfa AF: 0.395 Hom.: 962

Bravo AF: 0.632

Asia WGS AF: 0.685 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.71
Dann	Benign	0.44

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: rs2012725; hg19: chr22-38536861;