chrX-124190570-G-A

Variant names:

• chrX-124190570-G-A
• rs1279795
• ENST00000469481.1:n.453+186823G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B.

Score: -4 - Likely Benign

-4

BP4_Strong

The ENST00000469481.1(STAG2):​n.453+186823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.55 (12351 hom., 17905 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: STAG2 ENST00000469481.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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+186823G>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.550 AC: 60664 AN: 110358 Hom.: 12349 Cov.: 22

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.547

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.550 AC: 60701 AN: 110409 Hom.: 12351 Cov.: 22 AF XY: 0.548 AC XY: 17905 AN XY: 32677

African (AFR) AF: 0.663 AC: 20118 AN: 30352

American (AMR) AF: 0.616 AC: 6364 AN: 10334

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1390 AN: 2622

East Asian (EAS) AF: 0.830 AC: 2883 AN: 3474

South Asian (SAS) AF: 0.809 AC: 2101 AN: 2598

European-Finnish (FIN) AF: 0.406 AC: 2382 AN: 5867

Middle Eastern (MID) AF: 0.662 AC: 139 AN: 210

European-Non Finnish (NFE) AF: 0.456 AC: 24065 AN: 52780

Other (OTH) AF: 0.553 AC: 834 AN: 1508

Alfa AF: 0.502 Hom.: 47579

Bravo AF: 0.574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.49
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs1279795; hg19: chrX-123324420;