Variant 12-113369144-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173542.4(PLBD2):c.319G>A(p.Gly107Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PLBD2
NM_173542.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

Variant links:

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]

PLBD2 links:

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ACMG classification

Classification made for transcript

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=0.07909712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLBD2	NM_173542.4 link	c.319G>A	p.Gly107Ser	missense_variant	2/12	ENST00000280800.5	NP_775813.2	Q8NHP8-1
PLBD2	NM_001159727.2 link	c.319G>A	p.Gly107Ser	missense_variant	2/11		NP_001153199.1	Q8NHP8-2
PLBD2	XM_017018977.2 link	c.-9-3505G>A		intron_variant			XP_016874466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLBD2	ENST00000280800.5 link	c.319G>A	p.Gly107Ser	missense_variant	2/12	1	NM_173542.4	ENSP00000280800.3	Q8NHP8-1
PLBD2	ENST00000545182.6 link	c.319G>A	p.Gly107Ser	missense_variant	2/11	2		ENSP00000443463.2	Q8NHP8-2
PLBD2	ENST00000548997.1 link	n.138-3505G>A		intron_variant		3		ENSP00000450343.1	H0YIX0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452802

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.319G>A (p.G107S) alteration is located in exon 2 (coding exon 2) of the PLBD2 gene. This alteration results from a G to A substitution at nucleotide position 319, causing the glycine (G) at amino acid position 107 to be replaced by a serine (S). 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

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.0090

.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.69

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.059

Sift

Benign

0.62

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.0060

.;B

Vest4

0.14

MutPred

0.36

Loss of glycosylation at S106 (P = 0.0379);Loss of glycosylation at S106 (P = 0.0379);

MVP

0.20

MPC

0.36

ClinPred

0.22

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.44

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over