Variant 2-87753614-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_002665.4(PLGLB2):c.272C>A(p.Ala91Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0029 ( 17 hom., cov: 17)

Exomes 𝑓: 0.0022 ( 49 hom. )

Failed GnomAD Quality Control

Consequence

PLGLB2
NM_002665.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0660

Variant links:

Genes affected

PLGLB2 (HGNC:9073): (plasminogen like B2) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

PLGLB2 links:

PLGLB2 (HGNC:):

PLGLB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029583484).

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00215 (1077/500116) while in subpopulation AMR AF= 0.0338 (971/28736). AF 95% confidence interval is 0.032. There are 49 homozygotes in gnomad4_exome. There are 498 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLGLB2	NM_002665.4 linkuse as main transcript	c.272C>A	p.Ala91Glu	missense_variant	3/4	ENST00000359481.9	NP_002656.1	Q02325

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLGLB2	ENST00000359481.9 linkuse as main transcript	c.272C>A	p.Ala91Glu	missense_variant	3/4	1	NM_002665.4	ENSP00000352458.4	Q02325
PLGLB2	ENST00000465361.1 linkuse as main transcript	n.1243C>A		non_coding_transcript_exon_variant	2/3	1
PLGLB2	ENST00000410086.3 linkuse as main transcript	n.272C>A		non_coding_transcript_exon_variant	3/5	3		ENSP00000386317.3	Q02325
NCAL1	ENST00000646855.1 linkuse as main transcript	n.2809C>A		non_coding_transcript_exon_variant	20/22

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

346

AN:

120114

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000641

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000361

Gnomad OTH

AF:

0.00789

GnomAD3 exomes

AF:

0.00160

AC:

AN:

54334

Hom.:

AF XY:

0.00149

AC XY:

AN XY:

27546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00835

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000133

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00215

AC:

1077

AN:

500116

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

498

AN XY:

272596

show subpopulations

Gnomad4 AFR exome

AF:

0.000550

Gnomad4 AMR exome

AF:

0.0338

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00104

Gnomad4 SAS exome

AF:

0.0000176

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000569

Gnomad4 OTH exome

AF:

0.00191

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00288

AC:

346

AN:

120204

Hom.:

Cov.:

AF XY:

0.00377

AC XY:

215

AN XY:

57004

show subpopulations

Gnomad4 AFR

AF:

0.000376

Gnomad4 AMR

AF:

0.0320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000642

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000361

Gnomad4 OTH

AF:

0.00781

Alfa

AF:

0.00179

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

Jan 04, 2022

The c.272C>A (p.A91E) alteration is located in exon 3 (coding exon 3) of the PLGLB2 gene. This alteration results from a C to A substitution at nucleotide position 272, causing the alanine (A) at amino acid position 91 to be replaced by a glutamic acid (E). 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

0.19

BayesDel_addAF

Benign

0.00087

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.71

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0045

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.30

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

REVEL

Benign

0.29

Sift

Uncertain

0.010

Sift4G

Uncertain

0.010

Vest4

0.34

MutPred

0.57

Loss of MoRF binding (P = 0.0059);

MVP

0.70

ClinPred

0.038

GERP RS

0.53

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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