rs1556553319

Variant names:

• chrX-124076382-A-G
• rs1556553319
• NM_001042750.2:c.2584A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Moderate PP5_Moderate

The NM_001042750.2(STAG2):​c.2584A>G​(p.Arg862Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: STAG2 NM_001042750.2 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.79
• Publications: 1 publications found

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, Illumina, Labcorp Genetics (formerly Invitae), G2P
• Xq25 microduplication syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894
• PP5: Variant X-124076382-A-G is Pathogenic according to our data. Variant chrX-124076382-A-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 521058.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAG2	NM_001042750.2	c.2584A>G	p.Arg862Gly	missense_variant	Exon 26 of 35	ENST00000371145.8	NP_001036215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG2	ENST00000371145.8	c.2584A>G	p.Arg862Gly	missense_variant	Exon 26 of 35	1	NM_001042750.2	ENSP00000360187.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Pathogenic:1

Mar 17, 2017

Ambry Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	.;D;D;.;D
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	.;.;.;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.8	M;M;M;M;M
PhyloP100		4.8
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.9	D;D;D;D;D
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;D;D;D;D
Vest4		0.89
MutPred		0.73		Loss of stability (P = 0.0075);Loss of stability (P = 0.0075);Loss of stability (P = 0.0075);Loss of stability (P = 0.0075);Loss of stability (P = 0.0075);
MVP		0.98
MPC		2.6
ClinPred		1.0	D
GERP RS		1.5
Varity_R		0.97
gMVP		0.95
Mutation Taster		=12/88	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1556553319; hg19: chrX-123210232;