X-55077503-C-A

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

17

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)

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
PAGE2BNM_001015038.3 linkc.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
PAGE2BENST00000374971.2 linkc.298C>A p.Leu100Ile missense_variant Exon 4 of 5 1 NM_001015038.3 ENSP00000364110.1 Q5JRK9
PAGE2BENST00000374974.7 linkc.247C>A p.Leu83Ile missense_variant Exon 4 of 5 5 ENSP00000364113.3 Q5JRL0

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000218
AC:
4
AN:
183106
Hom.:
0
AF XY:
0.00
AC XY:
0
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:
7
AN:
1097838
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
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.:
23
Alfa
AF:
0.0000540
Hom.:
0
ExAC
AF:
0.0000330
AC:
4

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
T
BayesDel_noAF
Benign
-0.98
CADD
Benign
5.9
DANN
Benign
0.82
DEOGEN2
Benign
0.0059
.;T
FATHMM_MKL
Benign
0.0020
N
LIST_S2
Benign
0.62
T;T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.079
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.69
.;N
PrimateAI
Benign
0.43
T
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
T
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.

Other links and lift over

dbSNP: rs781620826; hg19: chrX-55103936; API