Genetic Variant STAG2:p.Thr42Ser (chrX-124030962-C-G) – 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_001042750.2(STAG2):c.125C>G(p.Thr42Ser) variant causes a missense, splice region 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. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

STAG2
NM_001042750.2 missense, splice_region

Scores

Splicing: ADA: 0.02130

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Mullegama-Klein-Martinez syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Xq25 microduplication syndrome
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

STAG2 links:

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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=0.16860989).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042750.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STAG2	NM_001042750.2	MANE Select	c.125C>G	p.Thr42Ser	missense splice_region	Exon 5 of 35	NP_001036215.1	Q8N3U4-2
STAG2	NM_001042749.2		c.125C>G	p.Thr42Ser	missense splice_region	Exon 5 of 35	NP_001036214.1	Q8N3U4-2
STAG2	NM_001375366.1		c.125C>G	p.Thr42Ser	missense splice_region	Exon 4 of 34	NP_001362295.1	Q8N3U4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STAG2	ENST00000371145.8	TSL:1 MANE Select	c.125C>G	p.Thr42Ser	missense splice_region	Exon 5 of 35	ENSP00000360187.4	Q8N3U4-2
STAG2	ENST00000218089.13	TSL:1	c.125C>G	p.Thr42Ser	missense splice_region	Exon 5 of 35	ENSP00000218089.9	Q8N3U4-2
STAG2	ENST00000371144.7	TSL:1	c.125C>G	p.Thr42Ser	missense splice_region	Exon 5 of 34	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.61

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

2.1

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.032

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.027

Vest4

0.17

MutPred

0.18

Loss of sheet (P = 0.0457)

MVP

0.52

MPC

1.0

ClinPred

0.37

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.53

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.021

dbscSNV1_RF

Benign

0.16

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over