chr2-200533001-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152524.6(SGO2):​c.26G>T​(p.Gly9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SGO2 NM_152524.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 21 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12394145).

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>T	p.Gly9Val	missense	Exon 2 of 9	NP_689737.4	Q562F6-1
	SGO2	NM_001160046.1		c.26G>T	p.Gly9Val	missense	Exon 2 of 9	NP_001153518.1	Q562F6-2
	SGO2	NM_001160033.1		c.26G>T	p.Gly9Val	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>T	p.Gly9Val	missense	Exon 2 of 9	ENSP00000350447.4	Q562F6-1
	SGO2	ENST00000409203.3	TSL:1	c.26G>T	p.Gly9Val	missense	Exon 2 of 6	ENSP00000386249.3	Q562F6-3
	SGO2	ENST00000921538.1		c.26G>T	p.Gly9Val	missense	Exon 3 of 10	ENSP00000591597.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245606 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: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457910 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725016

African (AFR) AF: 0.00 AC: 0 AN: 33252

American (AMR) AF: 0.00 AC: 0 AN: 43980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.00 AC: 0 AN: 84974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110850

Other (OTH) AF: 0.00 AC: 0 AN: 60238

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.21
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.083
Sift	Benign	0.10	T
Sift4G	Uncertain	0.053	T
Polyphen		0.76	P
Vest4		0.13
MutPred		0.28		Loss of sheet (P = 0.0315)
MVP		0.30
MPC		0.31
ClinPred		0.85	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.056
gMVP		0.028
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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;