X-124084669-T-G

Variant summary

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

The NM_001042750.2(STAG2):c.3053+1120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 111,708 control chromosomes in the GnomAD database, including 1,437 homozygotes. There are 5,871 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 0.18 (1437 hom., 5871 hem., cov: 23)
• Consequence: STAG2 NM_001042750.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAG2	NM_001042750.2	c.3053+1120T>G		intron_variant		ENST00000371145.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG2	ENST00000371145.8	c.3053+1120T>G		intron_variant		1	NM_001042750.2	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 20165 AN: 111653 Hom.: 1440 Cov.: 23 AF XY: 0.173 AC XY: 5861 AN XY: 33843

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.181 AC: 20168 AN: 111708 Hom.: 1437 Cov.: 23 AF XY: 0.173 AC XY: 5871 AN XY: 33908

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.168

Alfa AF: 0.166 Hom.: 3089

Bravo AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs5910058; hg19: chrX-123218519;