X-124025861-T-C

Variant names:

• chrX-124025861-T-C
• rs201477761
• NM_001042750.2:c.66T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001042750.2(STAG2):​c.66T>C​(p.Ser22Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,184,956 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 2 hem., cov: 21)
  • Exomes 𝑓: 0.0000093 (0 hom. 6 hem.)
• Consequence: STAG2 NM_001042750.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.43
• 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, G2P, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Xq25 microduplication syndrome

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant X-124025861-T-C is Benign according to our data. Variant chrX-124025861-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1622268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.43 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 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.66T>C	p.Ser22Ser	synonymous	Exon 4 of 35	NP_001036215.1	Q8N3U4-2
	STAG2	NM_001042749.2		c.66T>C	p.Ser22Ser	synonymous	Exon 4 of 35	NP_001036214.1	Q8N3U4-2
	STAG2	NM_001375366.1		c.66T>C	p.Ser22Ser	synonymous	Exon 3 of 34	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.66T>C	p.Ser22Ser	synonymous	Exon 4 of 35	ENSP00000360187.4	Q8N3U4-2
	STAG2	ENST00000218089.13	TSL:1	c.66T>C	p.Ser22Ser	synonymous	Exon 4 of 35	ENSP00000218089.9	Q8N3U4-2
	STAG2	ENST00000371144.7	TSL:1	c.66T>C	p.Ser22Ser	synonymous	Exon 4 of 34	ENSP00000360186.3	Q8N3U4-1

Frequencies

GnomAD3 genomes AF: 0.0000181 AC: 2 AN: 110440 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000379

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 2 AN: 167521 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000131

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000931 AC: 10 AN: 1074516 Hom.: 0 Cov.: 25 AF XY: 0.0000173 AC XY: 6 AN XY: 345930

African (AFR) AF: 0.00 AC: 0 AN: 25588

American (AMR) AF: 0.00 AC: 0 AN: 33143

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18895

East Asian (EAS) AF: 0.00 AC: 0 AN: 28993

South Asian (SAS) AF: 0.0000201 AC: 1 AN: 49787

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40017

Middle Eastern (MID) AF: 0.000246 AC: 1 AN: 4059

European-Non Finnish (NFE) AF: 0.00000965 AC: 8 AN: 828994

Other (OTH) AF: 0.00 AC: 0 AN: 45040

GnomAD4 genome AF: 0.0000181 AC: 2 AN: 110440 Hom.: 0 Cov.: 21 AF XY: 0.0000612 AC XY: 2 AN XY: 32698

African (AFR) AF: 0.00 AC: 0 AN: 30531

American (AMR) AF: 0.00 AC: 0 AN: 10196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3567

South Asian (SAS) AF: 0.00 AC: 0 AN: 2697

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.0000379 AC: 2 AN: 52806

Other (OTH) AF: 0.00 AC: 0 AN: 1481

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely 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	-0.53
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=294/6	polymorphism

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: rs201477761; hg19: chrX-123159711;