2-87753569-T-C

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

2
7
7

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

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
PLGLB2NM_002665.4 linkc.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 Appris UniProt
PLGLB2ENST00000359481.9 linkc.227T>C p.Met76Thr missense_variant Exon 3 of 4 1 NM_002665.4 ENSP00000352458.4 Q02325
PLGLB2ENST00000465361.1 linkn.1198T>C non_coding_transcript_exon_variant Exon 2 of 3 1
PLGLB2ENST00000410086.3 linkn.227T>C non_coding_transcript_exon_variant Exon 3 of 5 3 ENSP00000386317.3 Q02325
NCAL1ENST00000646855.1 linkn.2764T>C non_coding_transcript_exon_variant Exon 20 of 22

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
1
AN:
97942
Hom.:
0
Cov.:
12
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:
2
AN:
542656
Hom.:
0
Cov.:
6
AF XY:
0.00000340
AC XY:
1
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:
1
AN:
97942
Hom.:
0
Cov.:
12
AF XY:
0.00
AC XY:
0
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
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
19
DANN
Benign
0.95
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.16
N
M_CAP
Pathogenic
0.74
D
MetaRNN
Uncertain
0.46
T
MetaSVM
Uncertain
-0.21
T
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.0050
D
Vest4
0.32
MutPred
0.54
Loss of stability (P = 0.0722);
MVP
0.79
ClinPred
0.50
D
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.

Other links and lift over

dbSNP: rs1684667819; hg19: chr2-88053088; API