X-124022370-CAAAAA-CAA

Variant names:

• chrX-124022370-CAAA-C
• rs5903652
• NM_001042750.2:c.-97-147_-97-145delAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001042750.2(STAG2):​c.-97-147_-97-145delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00031 (0 hom., 0 hem., cov: 0)
• Consequence: STAG2 NM_001042750.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.-97-147_-97-145delAAA		intron	N/A	NP_001036215.1	Q8N3U4-2
	STAG2	NM_001042749.2		c.-97-147_-97-145delAAA		intron	N/A	NP_001036214.1	Q8N3U4-2
	STAG2	NM_001375366.1		c.-97-147_-97-145delAAA		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.-97-160_-97-158delAAA		intron	N/A	ENSP00000360187.4	Q8N3U4-2
	STAG2	ENST00000218089.13	TSL:1	c.-97-160_-97-158delAAA		intron	N/A	ENSP00000218089.9	Q8N3U4-2
	STAG2	ENST00000371144.7	TSL:1	c.-97-160_-97-158delAAA		intron	N/A	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes AF: 0.000305 AC: 24 AN: 78580 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000470

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000579

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00425

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000200

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000305 AC: 24 AN: 78580 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14512

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000470 AC: 1 AN: 21279

American (AMR) AF: 0.000579 AC: 4 AN: 6906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2025

East Asian (EAS) AF: 0.00 AC: 0 AN: 2602

South Asian (SAS) AF: 0.00 AC: 0 AN: 1579

European-Finnish (FIN) AF: 0.00425 AC: 11 AN: 2591

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 182

European-Non Finnish (NFE) AF: 0.000200 AC: 8 AN: 39902

Other (OTH) AF: 0.00 AC: 0 AN: 1022

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.016
Mutation Taster		=100/0	polymorphism

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;