X-124116647-G-A

Variant names:

• chrX-124116647-G-A
• rs5958390
• ENST00000469481.1:n.453+112900G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000469481.1(STAG2):​n.453+112900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (18331 hom., 21663 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: STAG2 ENST00000469481.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• 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, Illumina, Labcorp Genetics (formerly Invitae), G2P
• Xq25 microduplication syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000469481.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG2	ENST00000469481.1	TSL:3	n.453+112900G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.673 AC: 73958 AN: 109901 Hom.: 18345 Cov.: 22

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.689

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.676

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: 0.673 AC: 73964 AN: 109952 Hom.: 18331 Cov.: 22 AF XY: 0.672 AC XY: 21663 AN XY: 32224

African (AFR) AF: 0.467 AC: 14097 AN: 30198

American (AMR) AF: 0.712 AC: 7317 AN: 10278

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2032 AN: 2635

East Asian (EAS) AF: 0.793 AC: 2756 AN: 3477

South Asian (SAS) AF: 0.591 AC: 1534 AN: 2596

European-Finnish (FIN) AF: 0.729 AC: 4125 AN: 5655

Middle Eastern (MID) AF: 0.695 AC: 148 AN: 213

European-Non Finnish (NFE) AF: 0.765 AC: 40325 AN: 52727

Other (OTH) AF: 0.673 AC: 1009 AN: 1499

Alfa AF: 0.726 Hom.: 8956

Bravo AF: 0.663

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5958390; hg19: chrX-123250497;