Variant chr22-38111811-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.82

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	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 linkuse as main transcript	c.*350C>A		3_prime_UTR_variant	17/17	1	NM_003560.4	P3	O60733-1

Frequencies

GnomAD3 genomes

AF:

0.0969

AC:

14738

AN:

152068

Hom.:

798

Cov.:

show subpopulations

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.:

AF XY:

0.103

AC XY:

12138

AN XY:

117306

show subpopulations

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.:

AF XY:

0.0946

AC XY:

7035

AN XY:

74398

show subpopulations

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.:

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over