Genetic Variant PAGE2:p.Arg37Cys (chrX-55090526-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207339.4(PAGE2):c.109C>T(p.Arg37Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,203,738 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

PAGE2
NM_207339.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145

Publications

0 publications found

Variant links:

Genes affected

PAGE2 (HGNC:31804): (PAGE family member 2)

PAGE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13990894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207339.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAGE2	NM_207339.4	MANE Select	c.109C>T	p.Arg37Cys	missense	Exon 3 of 5	NP_997222.1	Q7Z2X7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAGE2	ENST00000374968.9	TSL:1 MANE Select	c.109C>T	p.Arg37Cys	missense	Exon 3 of 5	ENSP00000364107.4	Q7Z2X7
PAGE2	ENST00000374965.5	TSL:2	c.109C>T	p.Arg37Cys	missense	Exon 3 of 5	ENSP00000364104.1	X6R922
PAGE2	ENST00000449097.1	TSL:3	c.109C>T	p.Arg37Cys	missense	Exon 3 of 3	ENSP00000392976.1	X6RD31

Frequencies

GnomAD3 genomes

AF:

0.00000912

AC:

AN:

109674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000968

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

GnomAD2 exomes

AF:

0.00000563

AC:

AN:

177664

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1094064

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25814

American (AMR)

AF:

0.0000285

AC:

AN:

35037

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19314

East Asian (EAS)

AF:

0.00

AC:

AN:

30175

South Asian (SAS)

AF:

0.00

AC:

AN:

53413

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40143

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4119

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

840158

Other (OTH)

AF:

0.00

AC:

AN:

45891

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000912

AC:

AN:

109674

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29372

American (AMR)

AF:

0.0000968

AC:

AN:

10335

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3535

South Asian (SAS)

AF:

0.00

AC:

AN:

2624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5807

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52953

Other (OTH)

AF:

0.00

AC:

AN:

1483

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.74

M_CAP

Benign

0.0017

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.14

PROVEAN

Benign

-2.2

REVEL

Benign

0.013

Sift

Benign

0.048

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.24

MutPred

0.41

Loss of solvent accessibility (P = 0.0404)

MVP

0.19

MPC

0.28

ClinPred

0.77

GERP RS

-0.16

Varity_R

0.092

gMVP

0.018

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over