2-87748175-C-A

Position:

• chr2-87748175-C-A

Variant summary

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

The NM_002665.4(PLGLB2):​c.22C>A​(p.Leu8Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 18)
• Consequence: PLGLB2 NM_002665.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0620

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=0.32770342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLGLB2	NM_002665.4	c.22C>A	p.Leu8Ile	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.22C>A	p.Leu8Ile	missense_variant	1/4	1	NM_002665.4	ENSP00000352458.4
PLGLB2	ENST00000410086.3	n.22C>A		non_coding_transcript_exon_variant	1/5	3		ENSP00000386317.3
NCAL1	ENST00000646855.1	n.2586+399C>A		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

Dec 02, 2022

The c.22C>A (p.L8I) alteration is located in exon 1 (coding exon 1) of the PLGLB2 gene. This alteration results from a C to A substitution at nucleotide position 22, causing the leucine (L) at amino acid position 8 to be replaced by an isoleucine (I). 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	0.089
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Uncertain	0.98
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.0090	N
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.81	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.065
Sift	Benign	0.051	T
Sift4G	Benign	0.084	T
Vest4		0.31
MutPred		0.47		Gain of methylation at K4 (P = 0.1061);
MVP		0.79
ClinPred		0.12	T
GERP RS		-0.27
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-88047694;