X-124084669-T-G

Variant names:

• chrX-124084669-T-G
• rs5910058
• NM_001042750.2:c.3053+1120T>G

Variant summary

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG2	NM_001042750.2	MANE Select	c.3053+1120T>G		intron	N/A	NP_001036215.1
	STAG2	NM_001042749.2		c.3053+1120T>G		intron	N/A	NP_001036214.1
	STAG2	NM_001375366.1		c.3053+1120T>G		intron	N/A	NP_001362295.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG2	ENST00000371145.8	TSL:1 MANE Select	c.3053+1120T>G		intron	N/A	ENSP00000360187.4
	STAG2	ENST00000218089.13	TSL:1	c.3053+1120T>G		intron	N/A	ENSP00000218089.9
	STAG2	ENST00000371144.7	TSL:1	c.3053+1120T>G		intron	N/A	ENSP00000360186.3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 20165 AN: 111653 Hom.: 1440 Cov.: 23

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

African (AFR) AF: 0.224 AC: 6894 AN: 30739

American (AMR) AF: 0.129 AC: 1354 AN: 10519

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 327 AN: 2642

East Asian (EAS) AF: 0.391 AC: 1372 AN: 3513

South Asian (SAS) AF: 0.231 AC: 628 AN: 2714

European-Finnish (FIN) AF: 0.125 AC: 755 AN: 6042

Middle Eastern (MID) AF: 0.161 AC: 35 AN: 217

European-Non Finnish (NFE) AF: 0.155 AC: 8252 AN: 53136

Other (OTH) AF: 0.168 AC: 255 AN: 1516

Alfa AF: 0.168 Hom.: 4743

Bravo AF: 0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.41
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: rs5910058; hg19: chrX-123218519;