2-200533001-G-C

Variant names:

• chr2-200533001-G-C
• rs1036533
• NM_152524.6:c.26G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152524.6(SGO2):​c.26G>C​(p.Gly9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGO2 NM_152524.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 0 publications found

Genes affected

SGO2 (HGNC:30812): (shugoshin 2) Predicted to be involved in homologous chromosome segregation; meiotic sister chromatid cohesion; and mitotic sister chromatid segregation. Predicted to act upstream of or within meiotic nuclear division; positive regulation of maintenance of meiotic sister chromatid cohesion, centromeric; and protein localization. Located in chromosome, centromeric region and nuclear body. Part of mitotic cohesin complex. [provided by Alliance of Genome Resources, Apr 2022]

SGO2 Gene-Disease associations (from GenCC):

• Perrault syndrome

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049595863).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152524.6. 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
	SGO2	NM_152524.6	MANE Select	c.26G>C	p.Gly9Ala	missense	Exon 2 of 9	NP_689737.4	Q562F6-1
	SGO2	NM_001160046.1		c.26G>C	p.Gly9Ala	missense	Exon 2 of 9	NP_001153518.1	Q562F6-2
	SGO2	NM_001160033.1		c.26G>C	p.Gly9Ala	missense	Exon 2 of 9	NP_001153505.1	B7Z7S9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGO2	ENST00000357799.9	TSL:1 MANE Select	c.26G>C	p.Gly9Ala	missense	Exon 2 of 9	ENSP00000350447.4	Q562F6-1
	SGO2	ENST00000409203.3	TSL:1	c.26G>C	p.Gly9Ala	missense	Exon 2 of 6	ENSP00000386249.3	Q562F6-3
	SGO2	ENST00000921538.1		c.26G>C	p.Gly9Ala	missense	Exon 3 of 10	ENSP00000591597.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.21
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Benign	0.28	T
Sift4G	Benign	0.70	T
Polyphen		0.11	B
Vest4		0.088
MutPred		0.22		Gain of sheet (P = 0.0344)
MVP		0.14
MPC		0.084
ClinPred		0.053	T
GERP RS		1.3
Varity_R		0.034
gMVP		0.023
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1036533; hg19: chr2-201397724;