chrX-124025885-C-T

Variant names:

• chrX-124025885-C-T
• rs1255264404
• NM_001042750.2:c.90C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001042750.2(STAG2):​c.90C>T​(p.Ile30Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,073,840 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes 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: 0.0000056 (0 hom. 3 hem.)
• Consequence: STAG2 NM_001042750.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.296
• 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant X-124025885-C-T is Benign according to our data. Variant chrX-124025885-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1670622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.296 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL gene

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.90C>T	p.Ile30Ile	synonymous	Exon 4 of 35	NP_001036215.1	Q8N3U4-2
	STAG2	NM_001042749.2		c.90C>T	p.Ile30Ile	synonymous	Exon 4 of 35	NP_001036214.1	Q8N3U4-2
	STAG2	NM_001375366.1		c.90C>T	p.Ile30Ile	synonymous	Exon 3 of 34	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.90C>T	p.Ile30Ile	synonymous	Exon 4 of 35	ENSP00000360187.4	Q8N3U4-2
	STAG2	ENST00000218089.13	TSL:1	c.90C>T	p.Ile30Ile	synonymous	Exon 4 of 35	ENSP00000218089.9	Q8N3U4-2
	STAG2	ENST00000371144.7	TSL:1	c.90C>T	p.Ile30Ile	synonymous	Exon 4 of 34	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00 AC: 0 AN: 167332 AF XY: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000559 AC: 6 AN: 1073840 Hom.: 0 Cov.: 26 AF XY: 0.00000868 AC XY: 3 AN XY: 345634

African (AFR) AF: 0.00 AC: 0 AN: 25487

American (AMR) AF: 0.00 AC: 0 AN: 33111

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18858

East Asian (EAS) AF: 0.0000347 AC: 1 AN: 28836

South Asian (SAS) AF: 0.00 AC: 0 AN: 49765

European-Finnish (FIN) AF: 0.0000250 AC: 1 AN: 39983

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4046

European-Non Finnish (NFE) AF: 0.00000362 AC: 3 AN: 828701

Other (OTH) AF: 0.0000222 AC: 1 AN: 45053

GnomAD4 genome Cov.: 21

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	-0.30
CADD	Benign	5.4
DANN	Benign	0.72
PhyloP100		0.30

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: rs1255264404; hg19: chrX-123159735; COSMIC: COSV54353975;