chrX-55090566-C-T

Variant names:

• chrX-55090566-C-T
• rs779932459
• NM_207339.4:c.149C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_207339.4(PAGE2):​c.149C>T​(p.Ala50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,094,627 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000046 (0 hom. 4 hem.)
• Consequence: PAGE2 NM_207339.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0430

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAGE2	NM_207339.4	c.149C>T	p.Ala50Val	missense_variant	Exon 3 of 5	ENST00000374968.9	NP_997222.1
PAGE2	XM_017029353.2	c.149C>T	p.Ala50Val	missense_variant	Exon 3 of 5		XP_016884842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAGE2	ENST00000374968.9	c.149C>T	p.Ala50Val	missense_variant	Exon 3 of 5	1	NM_207339.4	ENSP00000364107.4
PAGE2	ENST00000449097.1	c.149C>T	p.Ala50Val	missense_variant	Exon 3 of 3	3		ENSP00000392976.1
PAGE2	ENST00000374965.5	c.142+7C>T		splice_region_variant, intron_variant	Intron 3 of 4	2		ENSP00000364104.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 0.0000167 AC: 3 AN: 180095 Hom.: 0 AF XY: 0.0000154 AC XY: 1 AN XY: 64927

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: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000457 AC: 5 AN: 1094627 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 4 AN XY: 360315

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: 0.0000932

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.149C>T (p.A50V) alteration is located in exon 3 (coding exon 2) of the PAGE2 gene. This alteration results from a C to T substitution at nucleotide position 149, causing the alanine (A) at amino acid position 50 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	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T;.
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.065
Sift	Benign	0.65	T;T
Sift4G	Benign	0.18	T;D
Polyphen		1.0	D;.
Vest4		0.062
MutPred		0.37		Gain of catalytic residue at A50 (P = 0.1449);Gain of catalytic residue at A50 (P = 0.1449);
MVP		0.22
MPC		0.26
ClinPred		0.33	T
GERP RS		-0.40
Varity_R		0.036
gMVP		0.0076

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.26		Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs779932459; hg19: chrX-55116999;