Genetic Variant PLGLB2:p.Met76Thr (chr2-87753569-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_002665.4(PLGLB2):c.227T>C(p.Met76Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000010 ( 0 hom., cov: 12)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLGLB2
NM_002665.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

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:

NCAL1 (HGNC:56663): (NK cell activity associated lncRNA 1)

NCAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLGLB2	NM_002665.4 link	c.227T>C	p.Met76Thr	missense_variant	Exon 3 of 4	ENST00000359481.9	NP_002656.1	Q02325

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLGLB2	ENST00000359481.9 link	c.227T>C	p.Met76Thr	missense_variant	Exon 3 of 4	1	NM_002665.4	ENSP00000352458.4	Q02325
PLGLB2	ENST00000465361.1 link	n.1198T>C		non_coding_transcript_exon_variant	Exon 2 of 3	1
PLGLB2	ENST00000410086.3 link	n.227T>C		non_coding_transcript_exon_variant	Exon 3 of 5	3		ENSP00000386317.3	Q02325
NCAL1	ENST00000646855.1 link	n.2764T>C		non_coding_transcript_exon_variant	Exon 20 of 22

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

97942

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000369

AC:

AN:

542656

Hom.:

Cov.:

AF XY:

0.00000340

AC XY:

AN XY:

294206

show subpopulations

Gnomad4 AFR exome

AF:

0.0000548

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:

0.00000325

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000102

AC:

AN:

97942

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

45524

show subpopulations

Gnomad4 AFR

AF:

0.0000305

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.227T>C (p.M76T) 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 227, causing the methionine (M) at amino acid position 76 to be replaced by a threonine (T). 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

0.18

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.16

M_CAP

Pathogenic

0.74

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

-0.21

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.49

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0050

Vest4

0.32

MutPred

0.54

Loss of stability (P = 0.0722);

MVP

0.79

ClinPred

0.50

GERP RS

0.53

gMVP

0.35

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