rs755194063

Variant names:

• chrX-124030948-A-G
• rs755194063
• NM_001042750.2:c.124-13A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-124030948-A-G
• chrX-124030948-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001042750.2(STAG2):​c.124-13A>G variant causes a intron 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: STAG2 NM_001042750.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990
• Publications: 0 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, G2P, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Xq25 microduplication syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-124030948-A-G is Benign according to our data. Variant chrX-124030948-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1584004.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG2	NM_001042750.2	MANE Select	c.124-13A>G		intron	N/A	NP_001036215.1	Q8N3U4-2
	STAG2	NM_001042749.2		c.124-13A>G		intron	N/A	NP_001036214.1	Q8N3U4-2
	STAG2	NM_001375366.1		c.124-13A>G		intron	N/A	NP_001362295.1	Q8N3U4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG2	ENST00000371145.8	TSL:1 MANE Select	c.124-13A>G		intron	N/A	ENSP00000360187.4	Q8N3U4-2
	STAG2	ENST00000218089.13	TSL:1	c.124-13A>G		intron	N/A	ENSP00000218089.9	Q8N3U4-2
	STAG2	ENST00000371144.7	TSL:1	c.124-13A>G		intron	N/A	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000670 AC: 1 AN: 149153 AF XY: 0.0000234

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000287

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1071990 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 345792

African (AFR) AF: 0.00 AC: 0 AN: 25184

American (AMR) AF: 0.00 AC: 0 AN: 30161

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17895

East Asian (EAS) AF: 0.00 AC: 0 AN: 29418

South Asian (SAS) AF: 0.00 AC: 0 AN: 49092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4007

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831482

Other (OTH) AF: 0.00 AC: 0 AN: 44929

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.065
DANN	Benign	0.48
PhyloP100		-0.099
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs755194063; hg19: chrX-123164798;