X-124022370-CAAAAA-CAAAA

Variant names:

• chrX-124022370-CA-C
• rs5903652
• NM_001042750.2:c.-97-145delA

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001042750.2(STAG2):​c.-97-145delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (25602 hom., 13132 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: STAG2 NM_001042750.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0160
• 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, G2P, Labcorp Genetics (formerly Invitae), Illumina
• Xq25 microduplication syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant X-124022370-CA-C is Benign according to our data. Variant chrX-124022370-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1243394.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.-97-145delA		intron	N/A	NP_001036215.1	Q8N3U4-2
	STAG2	NM_001042749.2		c.-97-145delA		intron	N/A	NP_001036214.1	Q8N3U4-2
	STAG2	NM_001375366.1		c.-97-145delA		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.-97-160delA		intron	N/A	ENSP00000360187.4	Q8N3U4-2
	STAG2	ENST00000218089.13	TSL:1	c.-97-160delA		intron	N/A	ENSP00000218089.9	Q8N3U4-2
	STAG2	ENST00000371144.7	TSL:1	c.-97-160delA		intron	N/A	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 70519 AN: 77972 Hom.: 25620 Cov.: 0

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.950

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.906

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.904 AC: 70480 AN: 77934 Hom.: 25602 Cov.: 0 AF XY: 0.948 AC XY: 13132 AN XY: 13848

African (AFR) AF: 0.754 AC: 15949 AN: 21166

American (AMR) AF: 0.939 AC: 6422 AN: 6836

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 1932 AN: 2002

East Asian (EAS) AF: 0.950 AC: 2436 AN: 2564

South Asian (SAS) AF: 0.977 AC: 1512 AN: 1548

European-Finnish (FIN) AF: 0.895 AC: 2322 AN: 2595

Middle Eastern (MID) AF: 0.962 AC: 153 AN: 159

European-Non Finnish (NFE) AF: 0.970 AC: 38360 AN: 39555

Other (OTH) AF: 0.906 AC: 930 AN: 1027

Alfa AF: 0.732 Hom.: 1272

ClinVar

ClinVar submissions as Germline

Significance: 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
PhyloP100		-0.016
Mutation Taster		=100/0	polymorphism (auto)

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: rs5903652; hg19: chrX-123156220;