chrX-124025825-A-C

Variant names:

• chrX-124025825-A-C
• rs781722799
• NM_001042750.2:c.45-15A>C

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.45-15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000099 in 1,010,453 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.9e-7 (0 hom. 0 hem.)
• Consequence: STAG2 NM_001042750.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.588
• 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, 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant X-124025825-A-C is Benign according to our data. Variant chrX-124025825-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2033767.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.45-15A>C		intron	N/A	NP_001036215.1	Q8N3U4-2
	STAG2	NM_001042749.2		c.45-15A>C		intron	N/A	NP_001036214.1	Q8N3U4-2
	STAG2	NM_001375366.1		c.45-15A>C		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.45-15A>C		intron	N/A	ENSP00000360187.4	Q8N3U4-2
	STAG2	ENST00000218089.13	TSL:1	c.45-15A>C		intron	N/A	ENSP00000218089.9	Q8N3U4-2
	STAG2	ENST00000371144.7	TSL:1	c.45-15A>C		intron	N/A	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.90e-7 AC: 1 AN: 1010453 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 299711

African (AFR) AF: 0.00 AC: 0 AN: 23705

American (AMR) AF: 0.00 AC: 0 AN: 28397

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17575

East Asian (EAS) AF: 0.00 AC: 0 AN: 28281

South Asian (SAS) AF: 0.00 AC: 0 AN: 43900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39367

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3851

European-Non Finnish (NFE) AF: 0.00000128 AC: 1 AN: 782736

Other (OTH) AF: 0.00 AC: 0 AN: 42641

GnomAD4 genome Cov.: 21

ClinVar

ClinVar submissions as Germline

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	-0.75
CADD	Benign	9.2
DANN	Benign	0.85
PhyloP100		0.59

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: rs781722799; hg19: chrX-123159675;