6-46705276-C-T

Variant names:

• chr6-46705276-C-T
• rs200015160
• NM_005084.4:c.1066G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005084.4(PLA2G7):​c.1066G>A​(p.Asp356Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D356G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

PLA2G7 (HGNC:9040): (phospholipase A2 group VII) The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2009]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.988

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1066G>A	p.Asp356Asn	missense_variant	Exon 11 of 12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2	c.1066G>A	p.Asp356Asn	missense_variant	Exon 11 of 12		NP_001161829.1
PLA2G7	XM_005249408.5	c.1066G>A	p.Asp356Asn	missense_variant	Exon 11 of 12		XP_005249465.1
PLA2G7	XM_047419359.1	c.931G>A	p.Asp311Asn	missense_variant	Exon 10 of 11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.1066G>A	p.Asp356Asn	missense_variant	Exon 11 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1066G>A	p.Asp356Asn	missense_variant	Exon 11 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.47	T;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Pathogenic	3.5	H;H
PhyloP100		7.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.4	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.94		Loss of catalytic residue at D356 (P = 0.0755);Loss of catalytic residue at D356 (P = 0.0755);
MVP		0.91
MPC		0.023
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.96
gMVP		0.95
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200015160; hg19: chr6-46673013;