chr2-200533001-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152524.6(SGO2):​c.26G>A​(p.Gly9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 1,609,184 control chromosomes in the GnomAD database, including 5,517 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.068 (509 hom., cov: 32)
  • Exomes 𝑓: 0.077 (5008 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013193488).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

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>A	p.Gly9Asp	missense	Exon 2 of 9	NP_689737.4	Q562F6-1
	SGO2	NM_001160046.1		c.26G>A	p.Gly9Asp	missense	Exon 2 of 9	NP_001153518.1	Q562F6-2
	SGO2	NM_001160033.1		c.26G>A	p.Gly9Asp	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>A	p.Gly9Asp	missense	Exon 2 of 9	ENSP00000350447.4	Q562F6-1
	SGO2	ENST00000409203.3	TSL:1	c.26G>A	p.Gly9Asp	missense	Exon 2 of 6	ENSP00000386249.3	Q562F6-3
	SGO2	ENST00000921538.1		c.26G>A	p.Gly9Asp	missense	Exon 3 of 10	ENSP00000591597.1

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10312 AN: 151628 Hom.: 507 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.0599

GnomAD2 exomes AF: 0.0884 AC: 21719 AN: 245606 AF XY: 0.0871

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.0609

Gnomad EAS exome AF: 0.0872

Gnomad FIN exome AF: 0.149

Gnomad NFE exome AF: 0.0764

Gnomad OTH exome AF: 0.0762

GnomAD4 exome AF: 0.0771 AC: 112315 AN: 1457438 Hom.: 5008 Cov.: 32 AF XY: 0.0777 AC XY: 56294 AN XY: 724774

African (AFR) AF: 0.0105 AC: 349 AN: 33252

American (AMR) AF: 0.145 AC: 6366 AN: 43936

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 1601 AN: 26006

East Asian (EAS) AF: 0.0819 AC: 3239 AN: 39554

South Asian (SAS) AF: 0.0743 AC: 6315 AN: 84952

European-Finnish (FIN) AF: 0.152 AC: 8108 AN: 53366

Middle Eastern (MID) AF: 0.0434 AC: 245 AN: 5650

European-Non Finnish (NFE) AF: 0.0737 AC: 81814 AN: 1110494

Other (OTH) AF: 0.0710 AC: 4278 AN: 60228

GnomAD4 genome AF: 0.0680 AC: 10318 AN: 151746 Hom.: 509 Cov.: 32 AF XY: 0.0713 AC XY: 5282 AN XY: 74112

African (AFR) AF: 0.0154 AC: 636 AN: 41386

American (AMR) AF: 0.0965 AC: 1472 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0600 AC: 208 AN: 3466

East Asian (EAS) AF: 0.0833 AC: 431 AN: 5174

South Asian (SAS) AF: 0.0665 AC: 319 AN: 4794

European-Finnish (FIN) AF: 0.155 AC: 1616 AN: 10444

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0789 AC: 5357 AN: 67920

Other (OTH) AF: 0.0597 AC: 126 AN: 2110

Alfa AF: 0.0719 Hom.: 1167

Bravo AF: 0.0620

TwinsUK AF: 0.0655 AC: 243

ALSPAC AF: 0.0776 AC: 299

ESP6500AA AF: 0.0139 AC: 50

ESP6500EA AF: 0.0696 AC: 566

ExAC AF: 0.0846 AC: 10221

Asia WGS AF: 0.0760 AC: 264 AN: 3470

EpiCase AF: 0.0720

EpiControl AF: 0.0689

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.66
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.21
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.086
Sift	Benign	0.96	T
Sift4G	Benign	0.56	T
Polyphen		0.0040	B
Vest4		0.031
MPC		0.080
ClinPred		0.00059	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.029
gMVP		0.019
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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; COSMIC: COSV63414198; COSMIC: COSV63414198;