NM_001042750.2:c.45-157A>G

Variant names:

• chrX-124025683-A-G
• rs79769028
• NM_001042750.2:c.45-157A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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, G2P, Labcorp Genetics (formerly Invitae), Illumina
• Xq25 microduplication syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 61 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042750.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG2	NM_001042750.2	MANE Select	c.45-157A>G		intron	N/A	NP_001036215.1	Q8N3U4-2
	STAG2	NM_001042749.2		c.45-157A>G		intron	N/A	NP_001036214.1	Q8N3U4-2
	STAG2	NM_001375366.1		c.45-157A>G		intron	N/A	NP_001362295.1	Q8N3U4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG2	ENST00000371145.8	TSL:1 MANE Select	c.45-157A>G		intron	N/A	ENSP00000360187.4	Q8N3U4-2
	STAG2	ENST00000218089.13	TSL:1	c.45-157A>G		intron	N/A	ENSP00000218089.9	Q8N3U4-2
	STAG2	ENST00000371144.7	TSL:1	c.45-157A>G		intron	N/A	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 3773 AN: 111509 Hom.: 61 Cov.: 21

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

African (AFR) AF: 0.0119 AC: 367 AN: 30848

American (AMR) AF: 0.0256 AC: 267 AN: 10432

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 55 AN: 2642

East Asian (EAS) AF: 0.000557 AC: 2 AN: 3590

South Asian (SAS) AF: 0.0168 AC: 45 AN: 2685

European-Finnish (FIN) AF: 0.0719 AC: 427 AN: 5935

Middle Eastern (MID) AF: 0.0276 AC: 6 AN: 217

European-Non Finnish (NFE) AF: 0.0483 AC: 2559 AN: 53012

Other (OTH) AF: 0.0290 AC: 44 AN: 1517

Alfa AF: 0.0402 Hom.: 227

Bravo AF: 0.0309

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.32
PhyloP100		-0.013
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79769028; hg19: chrX-123159533;