X-124025683-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001042750.2(STAG2):c.45-157A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 111,558 control chromosomes in the GnomAD database, including 61 homozygotes. There are 1,133 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.034 (61 hom., 1133 hem., cov: 21)
• Consequence: STAG2 NM_001042750.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-124025683-A-G is Benign according to our data. Variant chrX-124025683-A-G is described in ClinVar as [Benign]. Clinvar id is 1230217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0338 (3772/111558) while in subpopulation NFE AF= 0.0483 (2559/53012). AF 95% confidence interval is 0.0467. There are 61 homozygotes in gnomad4. There are 1133 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 61 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAG2	NM_001042750.2	c.45-157A>G		intron_variant		ENST00000371145.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAG2	ENST00000371145.8	c.45-157A>G		intron_variant		1	NM_001042750.2	P1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 3773 AN: 111509 Hom.: 61 Cov.: 21 AF XY: 0.0337 AC XY: 1135 AN XY: 33709

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0256

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.000555

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0483

Gnomad OTH AF: 0.0294

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

GnomAD4 genome AF: 0.0338 AC: 3772 AN: 111558 Hom.: 61 Cov.: 21 AF XY: 0.0336 AC XY: 1133 AN XY: 33768

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.000557

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0719

Gnomad4 NFE AF: 0.0483

Gnomad4 OTH AF: 0.0290

Alfa AF: 0.0402 Hom.: 227

Bravo AF: 0.0309

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.77
Dann	Benign	0.32

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: rs79769028; hg19: chrX-123159533;