Variant 2-87753563-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_002665.4(PLGLB2):c.221T>C(p.Val74Ala) 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 0.00039 ( 1 hom., cov: 12)

Exomes 𝑓: 0.00064 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PLGLB2
NM_002665.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.629

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31613356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLGLB2	NM_002665.4 linkuse as main transcript	c.221T>C	p.Val74Ala	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.221T>C	p.Val74Ala	missense_variant	3/4	1	NM_002665.4	ENSP00000352458.4	Q02325
PLGLB2	ENST00000465361.1 linkuse as main transcript	n.1192T>C		non_coding_transcript_exon_variant	2/3	1
PLGLB2	ENST00000410086.3 linkuse as main transcript	n.221T>C		non_coding_transcript_exon_variant	3/5	3		ENSP00000386317.3	Q02325
NCAL1	ENST00000646855.1 linkuse as main transcript	n.2758T>C		non_coding_transcript_exon_variant	20/22

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

98540

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000605

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

Gnomad ASJ

AF:

0.00552

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000468

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000625

AC:

AN:

16012

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

8352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000637

AC:

339

AN:

532266

Hom.:

Cov.:

AF XY:

0.000635

AC XY:

183

AN XY:

288098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000606

Gnomad4 ASJ exome

AF:

0.00655

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000256

Gnomad4 FIN exome

AF:

0.0000438

Gnomad4 NFE exome

AF:

0.000598

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000385

AC:

AN:

98668

Hom.:

Cov.:

AF XY:

0.000348

AC XY:

AN XY:

45932

show subpopulations

Gnomad4 AFR

AF:

0.0000603

Gnomad4 AMR

AF:

0.000134

Gnomad4 ASJ

AF:

0.00552

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000468

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000927

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

Apr 07, 2022

The c.221T>C (p.V74A) alteration is located in exon 3 (coding exon 3) of the PLGLB2 gene. This alteration results from a T to C substitution at nucleotide position 221, causing the valine (V) at amino acid position 74 to be replaced by an alanine (A). 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

0.20

BayesDel_addAF

Benign

-0.00079

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.0098

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.30

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.1

REVEL

Benign

0.18

Sift

Benign

0.14

Sift4G

Pathogenic

0.0

Vest4

0.16

MutPred

0.63

Loss of sheet (P = 0.0025);

MVP

0.86

ClinPred

0.037

GERP RS

0.53

gMVP

0.22

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