rs781017550

Variant names:

• chr12-113374962-C-G
• rs781017550
• NM_173542.4:c.814C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-113374962-C-G
• chr12-113374962-C-T

Variant summary

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

The NM_173542.4(PLBD2):​c.814C>G​(p.Arg272Gly) 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 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. R272H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLBD2 NM_173542.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• Publications: 0 publications found

Genes affected

PLBD2 (HGNC:27283): (phospholipase B domain containing 2) Predicted to enable phospholipase activity. Predicted to be involved in phospholipid catabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.99

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLBD2	NM_173542.4	c.814C>G	p.Arg272Gly	missense_variant	Exon 5 of 12	ENST00000280800.5	NP_775813.2
PLBD2	NM_001159727.2	c.814C>G	p.Arg272Gly	missense_variant	Exon 5 of 11		NP_001153199.1
PLBD2	XM_011538023.3	c.439C>G	p.Arg147Gly	missense_variant	Exon 4 of 11		XP_011536325.1
PLBD2	XM_017018977.2	c.421C>G	p.Arg141Gly	missense_variant	Exon 4 of 11		XP_016874466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLBD2	ENST00000280800.5	c.814C>G	p.Arg272Gly	missense_variant	Exon 5 of 12	1	NM_173542.4	ENSP00000280800.3
PLBD2	ENST00000545182.6	c.814C>G	p.Arg272Gly	missense_variant	Exon 5 of 11	2		ENSP00000443463.2
PLBD2	ENST00000547163.1	n.97C>G		non_coding_transcript_exon_variant	Exon 1 of 2	5
PLBD2	ENST00000548997.1	n.*408C>G		downstream_gene_variant		3		ENSP00000450343.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.5	M;M
PhyloP100		3.1
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.7	D;D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		1.0	.;D
Vest4		0.95
MutPred		0.93		Loss of MoRF binding (P = 0.0082);Loss of MoRF binding (P = 0.0082);
MVP		0.74
MPC		1.3
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.93
gMVP		0.99
Mutation Taster		=3/97	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs781017550; hg19: chr12-113812767;