rs587784356

Positions:

• chr22-38169423-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_003560.4(PLA2G6):​c.4C>A​(p.Gln2Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G6 NM_003560.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.27

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 22-38169423-G-T is Pathogenic according to our data. Variant chr22-38169423-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 159772.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G6	NM_003560.4	c.4C>A	p.Gln2Lys	missense_variant	2/17	ENST00000332509.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G6	ENST00000332509.8	c.4C>A	p.Gln2Lys	missense_variant	2/17	1	NM_003560.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Iron accumulation in brain Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;.;.;T;T;T;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;.;D;D;.;.;D;D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.4	M;M;M;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N;N;N;N;D;D;D;D;.
REVEL	Benign	0.25
Sift	Uncertain	0.012	D;D;D;D;D;D;D;D;D;.
Sift4G	Benign	0.11	T;T;T;T;T;D;D;D;.;.
Polyphen		0.97	D;P;P;.;.;.;.;.;.;.
Vest4		0.65
MutPred		0.31		Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);Gain of MoRF binding (P = 0.0115);
MVP		0.81
MPC		0.82
ClinPred		0.93	D
GERP RS		4.6
Varity_R		0.23
gMVP		0.69

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

Other links and lift over

dbSNP: rs587784356; hg19: chr22-38565430;