Genetic Variant GAGE2A:p.Met26Thr (chrX-49590727-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001127212.4(GAGE2A):c.77T>C(p.Met26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M26V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 145)

Failed GnomAD Quality Control

Consequence

GAGE2A
NM_001127212.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.617

Publications

0 publications found

Variant links:

Genes affected

GAGE2A (HGNC:4099): (G antigen 2A)

GAGE2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2782651).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAGE2A	NM_001127212.4 link	c.77T>C	p.Met26Thr	missense_variant	Exon 2 of 5	ENST00000362097.2	NP_001120684.1	Q6NT46

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAGE2A	ENST00000362097.2 link	c.77T>C	p.Met26Thr	missense_variant	Exon 2 of 5	1	NM_001127212.4	ENSP00000355421.1		Q6NT46

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

115093

Hom.:

Cov.:

145

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Cov.:

297

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

115147

Hom.:

Cov.:

145

AF XY:

0.00

AC XY:

AN XY:

37269

African (AFR)

AF:

0.00

AC:

AN:

31889

American (AMR)

AF:

0.00

AC:

AN:

11056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2670

East Asian (EAS)

AF:

0.00

AC:

AN:

3734

South Asian (SAS)

AF:

0.00

AC:

AN:

2994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6603

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53708

Other (OTH)

AF:

0.00

AC:

AN:

1583

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 30, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.77T>C (p.M26T) alteration is located in exon 2 (coding exon 1) of the GAGE2A gene. This alteration results from a T to C substitution at nucleotide position 77, causing the methionine (M) at amino acid position 26 to be replaced by a threonine (T). 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

0.32

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.021

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

0.62

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.059

Sift

Uncertain

0.024

Sift4G

Uncertain

0.026

Polyphen

0.97

Vest4

0.19

MVP

0.067

ClinPred

0.29

GERP RS

1.1

Varity_R

0.27

gMVP

0.017

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over