chr2-200572292-A-G

Position:

• chr2-200572292-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_152524.6(SGO2):​c.1946A>G​(p.Lys649Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGO2 NM_152524.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.73

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08587754).
• BP6: Variant 2-200572292-A-G is Benign according to our data. Variant chr2-200572292-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2651811.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGO2	NM_152524.6	c.1946A>G	p.Lys649Arg	missense_variant	7/9	ENST00000357799.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGO2	ENST00000357799.9	c.1946A>G	p.Lys649Arg	missense_variant	7/9	1	NM_152524.6	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000410 AC: 1 AN: 243828 Hom.: 0 AF XY: 0.00000753 AC XY: 1 AN XY: 132770

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000169

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

SGO2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.091
Sift	Benign	0.14	T
Sift4G	Benign	0.31	T
Polyphen		0.0040	B
Vest4		0.059
MutPred		0.31		Loss of methylation at K649 (P = 0.0011);
MVP		0.27
MPC		0.056
ClinPred		0.18	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.025
gMVP		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1559216992; hg19: chr2-201437015;