15-42142640-G-C

Position:

• chr15-42142640-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_213600.4(PLA2G4F):​c.2217C>G​(p.Asp739Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PLA2G4F NM_213600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.389

Genes affected

PLA2G4F (HGNC:27396): (phospholipase A2 group IVF) Predicted to enable calcium ion binding activity; calcium-dependent phospholipase A2 activity; and calcium-dependent phospholipid binding activity. Predicted to be involved in glycerophospholipid catabolic process. Predicted to act upstream of or within several processes, including arachidonic acid secretion; cellular response to antibiotic; and prostaglandin biosynthetic process. Predicted to be located in cytoplasm. Predicted to be active in cytosol; ruffle membrane; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11414376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4F	NM_213600.4	c.2217C>G	p.Asp739Glu	missense_variant	19/20	ENST00000397272.7	NP_998765.3
PLA2G4F	NR_033151.2	n.2231C>G		non_coding_transcript_exon_variant	18/19
PLA2G4F	XR_931785.1	n.2420C>G		non_coding_transcript_exon_variant	20/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4F	ENST00000397272.7	c.2217C>G	p.Asp739Glu	missense_variant	19/20	1	NM_213600.4	ENSP00000380442	P1
PLA2G4F	ENST00000290497.11	c.*1961C>G		3_prime_UTR_variant, NMD_transcript_variant	18/19	1		ENSP00000290497
PLA2G4F	ENST00000562320.1	c.*22C>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	1		ENSP00000455037
PLA2G4F	ENST00000569985.5	c.*1261C>G		3_prime_UTR_variant, NMD_transcript_variant	19/20	1		ENSP00000454330

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.2217C>G (p.D739E) alteration is located in exon 19 (coding exon 19) of the PLA2G4F gene. This alteration results from a C to G substitution at nucleotide position 2217, causing the aspartic acid (D) at amino acid position 739 to be replaced by a glutamic acid (E). 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.94	L
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.40	T
REVEL	Benign	0.068
Sift4G	Benign	0.43	T
Polyphen		0.98	D
Vest4		0.26
MVP		0.39
ClinPred		0.90	D
GERP RS		2.8
Varity_R		0.094
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42434838;