Genetic Variant PAGE2B:p.Leu100Ile (chrX-55077503-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001015038.3(PAGE2B):c.298C>A(p.Leu100Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,838 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000064 ( 0 hom. 0 hem. )

Consequence

PAGE2B
NM_001015038.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.239

Variant links:

Genes affected

PAGE2B (HGNC:31805): (PAGE family member 2B)

PAGE2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07862738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE2B	NM_001015038.3 link	c.298C>A	p.Leu100Ile	missense_variant	Exon 4 of 5	ENST00000374971.2	NP_001015038.1	Q5JRK9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE2B	ENST00000374971.2 link	c.298C>A	p.Leu100Ile	missense_variant	Exon 4 of 5	1	NM_001015038.3	ENSP00000364110.1		Q5JRK9
PAGE2B	ENST00000374974.7 link	c.247C>A	p.Leu83Ile	missense_variant	Exon 4 of 5	5		ENSP00000364113.3		Q5JRL0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183106

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67680

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:

0.0000490

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000831

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000540

Hom.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298C>A (p.L100I) alteration is located in exon 4 (coding exon 3) of the PAGE2B gene. This alteration results from a C to A substitution at nucleotide position 298, causing the leucine (L) at amino acid position 100 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

0.096

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.98

CADD

Benign

5.9

DANN

Benign

0.82

DEOGEN2

Benign

0.0059

.;T

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

.;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.011

Sift

Benign

0.048

D;T

Sift4G

Benign

0.22

T;T

Polyphen

0.12

.;B

Vest4

0.13

MutPred

0.27

.;Gain of methylation at K102 (P = 0.0811);

MVP

0.014

MPC

0.57

ClinPred

0.025

GERP RS

-1.9

Varity_R

0.087

gMVP

0.0025

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