22-38111811-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003560.4(PLA2G6):c.*350C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 369,066 control chromosomes in the GnomAD database, including 1,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.097 (800 hom., cov: 33)
  • Exomes 𝑓: 0.099 (1194 hom.)
• Consequence: PLA2G6 NM_003560.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-38111811-G-T is Benign according to our data. Variant chr22-38111811-G-T is described in ClinVar as [Benign]. Clinvar id is 341629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G6	NM_003560.4	c.*350C>A		3_prime_UTR_variant	17/17	ENST00000332509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000332509.8	c.*350C>A		3_prime_UTR_variant	17/17	1	NM_003560.4	P3

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14738 AN: 152068 Hom.: 798 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0740

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0992 AC: 21513 AN: 216880 Hom.: 1194 Cov.: 0 AF XY: 0.103 AC XY: 12138 AN XY: 117306

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0589

Gnomad4 ASJ exome AF: 0.0901

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0554

Gnomad4 NFE exome AF: 0.0895

Gnomad4 OTH exome AF: 0.0951

GnomAD4 genome AF: 0.0969 AC: 14742 AN: 152186 Hom.: 800 Cov.: 33 AF XY: 0.0946 AC XY: 7035 AN XY: 74398

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0876

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0263 Hom.: 12

Bravo AF: 0.0999

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PLA2G6-associated neurodegeneration Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.14
Dann	Benign	0.54

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: rs11570770; hg19: chr22-38507818; COSMIC: COSV59273871; COSMIC: COSV59273871;