rs1846322

Variant names:

• chrX-124181529-C-T
• rs1846322
• ENST00000469481.1:n.453+177782C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000469481.1(STAG2):​n.453+177782C>T variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAG2	ENST00000469481.1	n.453+177782C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 35523 AN: 111271 Hom.: 4429 Cov.: 23

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

African (AFR) AF: 0.216 AC: 6628 AN: 30733

American (AMR) AF: 0.446 AC: 4647 AN: 10416

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 965 AN: 2647

East Asian (EAS) AF: 0.542 AC: 1913 AN: 3528

South Asian (SAS) AF: 0.555 AC: 1480 AN: 2669

European-Finnish (FIN) AF: 0.245 AC: 1458 AN: 5954

Middle Eastern (MID) AF: 0.488 AC: 104 AN: 213

European-Non Finnish (NFE) AF: 0.333 AC: 17618 AN: 52977

Other (OTH) AF: 0.336 AC: 507 AN: 1509

Alfa AF: 0.340 Hom.: 32877

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
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs1846322; hg19: chrX-123315379;