2-87748190-T-G

Position:

• chr2-87748190-T-G

Variant summary

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

The NM_002665.4(PLGLB2):​c.37T>G​(p.Phe13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 18)
• Consequence: PLGLB2 NM_002665.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17

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:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29918995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLGLB2	NM_002665.4	c.37T>G	p.Phe13Val	missense_variant	1/4	ENST00000359481.9	NP_002656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLGLB2	ENST00000359481.9	c.37T>G	p.Phe13Val	missense_variant	1/4	1	NM_002665.4	ENSP00000352458.4
PLGLB2	ENST00000410086.3	n.37T>G		non_coding_transcript_exon_variant	1/5	3		ENSP00000386317.3
NCAL1	ENST00000646855.1	n.2586+414T>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 9

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2024

The c.37T>G (p.F13V) alteration is located in exon 1 (coding exon 1) of the PLGLB2 gene. This alteration results from a T to G substitution at nucleotide position 37, causing the phenylalanine (F) at amino acid position 13 to be replaced by a valine (V). 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	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.97
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.20	N
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.96	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.089
Sift	Benign	0.11	T
Sift4G	Uncertain	0.035	D
Vest4		0.33
MutPred		0.44		Loss of catalytic residue at F13 (P = 0.0418);
MVP		0.74
ClinPred		0.60	D
GERP RS		0.81
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-88047709;