Variant 15-42070038-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178034.4(PLA2G4D):c.2101G>C(p.Glu701Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,519,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PLA2G4D
NM_178034.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.104

Variant links:

Genes affected

PLA2G4D (HGNC:30038): (phospholipase A2 group IVD) The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).[supplied by OMIM, Jun 2009]

PLA2G4D links:

PLA2G4D (HGNC:):

PLA2G4D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040649116).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4D	NM_178034.4 linkuse as main transcript	c.2101G>C	p.Glu701Gln	missense_variant	19/20	ENST00000290472.4	NP_828848.3	Q86XP0-1
PLA2G4D	XM_047432399.1 linkuse as main transcript	c.2101G>C	p.Glu701Gln	missense_variant	19/20		XP_047288355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4D	ENST00000290472.4 linkuse as main transcript	c.2101G>C	p.Glu701Gln	missense_variant	19/20	1	NM_178034.4	ENSP00000290472.3		Q86XP0-1
PLA2G4D	ENST00000560932.1 linkuse as main transcript	n.1254G>C		non_coding_transcript_exon_variant	4/5	1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

125432

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67020

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1366998

Hom.:

Cov.:

AF XY:

0.00000891

AC XY:

AN XY:

673556

show subpopulations

Gnomad4 AFR exome

AF:

0.000413

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000530

GnomAD4 genome

AF:

0.000125

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000136

ExAC

AF:

0.0000104

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.2101G>C (p.E701Q) alteration is located in exon 19 (coding exon 19) of the PLA2G4D gene. This alteration results from a G to C substitution at nucleotide position 2101, causing the glutamic acid (E) at amino acid position 701 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.039

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.18

M_CAP

Benign

0.0021

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

REVEL

Benign

0.051

Sift

Benign

0.22

Sift4G

Benign

0.23

Polyphen

0.017

Vest4

0.17

MVP

0.49

MPC

0.062

ClinPred

0.056

GERP RS

4.2

Varity_R

0.25

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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