rs1781115

Variant names:

• chrX-124186482-T-C
• rs1781115
• ENST00000469481.1:n.453+182735T>C

Variant summary

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

The ENST00000469481.1(STAG2):​n.453+182735T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 111,751 control chromosomes in the GnomAD database, including 8,367 homozygotes. There are 14,758 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 0.44 (8367 hom., 14758 hem., cov: 24)
• Consequence: STAG2 ENST00000469481.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 1 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 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+182735T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 49077 AN: 111696 Hom.: 8366 Cov.: 24

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.439 AC: 49108 AN: 111751 Hom.: 8367 Cov.: 24 AF XY: 0.434 AC XY: 14758 AN XY: 33969

African (AFR) AF: 0.577 AC: 17736 AN: 30747

American (AMR) AF: 0.528 AC: 5558 AN: 10518

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1082 AN: 2646

East Asian (EAS) AF: 0.737 AC: 2599 AN: 3527

South Asian (SAS) AF: 0.696 AC: 1902 AN: 2734

European-Finnish (FIN) AF: 0.260 AC: 1576 AN: 6064

Middle Eastern (MID) AF: 0.507 AC: 110 AN: 217

European-Non Finnish (NFE) AF: 0.333 AC: 17672 AN: 53102

Other (OTH) AF: 0.438 AC: 667 AN: 1522

Alfa AF: 0.384 Hom.: 43684

Bravo AF: 0.470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.85
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs1781115; hg19: chrX-123320332;