Variant chrX-124022632-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001042750.2(STAG2):c.5T>C(p.Ile2Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

STAG2
NM_001042750.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45

Variant links:

Genes affected

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

STAG2 links:

STAG2 (HGNC:):

STAG2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), STAG2. . Gene score misZ 4.938 (greater than the threshold 3.09). GenCC has associacion of gene with Mullegama-Klein-Martinez syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAG2	NM_001042750.2 linkuse as main transcript	c.5T>C	p.Ile2Thr	missense_variant	3/35	ENST00000371145.8	NP_001036215.1	Q8N3U4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAG2	ENST00000371145.8 linkuse as main transcript	c.5T>C	p.Ile2Thr	missense_variant	3/35	1	NM_001042750.2	ENSP00000360187.4		Q8N3U4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mullegama-Klein-Martinez syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Sep 19, 2020

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0090

.;T;.;.;T;.;T;.;T;.;.;T

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

D;D;.;D;.;D;.;D;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.54

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.81

.;.;L;.;L;.;L;L;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-5.0

D;N;N;D;N;N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;.;D;D;D;D;D;D;D;D

Polyphen

0.99, 0.0040

.;.;D;.;B;.;B;D;B;.;.;.

Vest4

0.62, 0.67, 0.68, 0.64, 0.67

MutPred

0.40

Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);Gain of glycosylation at I2 (P = 0.0019);

MVP

0.39

MPC

2.6

ClinPred

0.99

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.75

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