rs1846322

chrX-124181529-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000469481.1(STAG2):n.453+177782C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 111,322 control chromosomes in the GnomAD database, including 4,431 homozygotes. There are 10,622 hemizygotes in GnomAD. 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 0.32 (4431 hom., 10622 hem., cov: 23)
• Consequence: STAG2 ENST00000469481.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG2	ENST00000469481.1	n.453+177782C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 35523 AN: 111271 Hom.: 4429 Cov.: 23 AF XY: 0.316 AC XY: 10604 AN XY: 33507

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.496

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.319 AC: 35542 AN: 111322 Hom.: 4431 Cov.: 23 AF XY: 0.316 AC XY: 10622 AN XY: 33568

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.336

Alfa AF: 0.348 Hom.: 26455

Bravo AF: 0.330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	10
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1846322; hg19: chrX-123315379;