2-28532190-A-G

Variant names:

• chr2-28532190-A-G
• NM_153021.5:c.551A>G

Variant summary

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

The NM_153021.5(PLB1):​c.551A>G​(p.Gln184Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLB1 NM_153021.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

Genes affected

PLB1 (HGNC:30041): (phospholipase B1) This gene encodes a membrane-associated phospholipase that displays lysophospholipase and phospholipase A2 activities through removal of sn-1 and sn-2 fatty acids of glycerophospholipids. In addition, it displays lipase and retinyl ester hydrolase activities. The encoded protein is highly conserved and is composed of a large, glycosylated extracellular domain composed of four tandem homologous domains, followed by a hydrophobic segment that anchors the enzyme to the membrane and a short C-terminal cytoplasmic tail. This gene has been identified as a candidate rheumatoid arthritis risk gene. [provided by RefSeq, Jul 2016]

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=0.13915583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLB1	NM_153021.5	c.551A>G	p.Gln184Arg	missense_variant	Exon 9 of 58	ENST00000327757.10	NP_694566.4
PLB1	NM_001170585.2	c.551A>G	p.Gln184Arg	missense_variant	Exon 9 of 57		NP_001164056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLB1	ENST00000327757.10	c.551A>G	p.Gln184Arg	missense_variant	Exon 9 of 58	1	NM_153021.5	ENSP00000330442.5
PLB1	ENST00000422425.6	c.551A>G	p.Gln184Arg	missense_variant	Exon 9 of 57	1		ENSP00000416440.2
PLB1	ENST00000404858.5	c.545A>G	p.Gln182Arg	missense_variant	Exon 9 of 57	1		ENSP00000384187.1
PLB1	ENST00000416713.5	c.383A>G	p.Gln128Arg	missense_variant	Exon 9 of 11	5		ENSP00000407076.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.551A>G (p.Q184R) alteration is located in exon 9 (coding exon 9) of the PLB1 gene. This alteration results from a A to G substitution at nucleotide position 551, causing the glutamine (Q) at amino acid position 184 to be replaced by an arginine (R). 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	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.070
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.33	T;D;D
Polyphen		0.56, 0.90	.;P;P
Vest4		0.41, 0.47
MutPred		0.29		.;Loss of glycosylation at P181 (P = 0.1244);Loss of glycosylation at P181 (P = 0.1244);
MVP		0.13
MPC		0.050
ClinPred		0.63	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-28755057;