13-45713656-G-A

Variant names:

• chr13-45713656-G-A
• NM_152719.3:c.631G>A

Variant summary

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

The NM_152719.3(CBY2):​c.631G>A​(p.Glu211Lys) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBY2 NM_152719.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34
• Publications: 0 publications found

Genes affected

CBY2 (HGNC:30720): (chibby family member 2) Enables identical protein binding activity. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12012425).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152719.3. 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
	CBY2	NM_152719.3	MANE Select	c.631G>A	p.Glu211Lys	missense	Exon 3 of 3	NP_689932.1	Q8NA61-1
	CBY2	NM_001286341.2		c.550G>A	p.Glu184Lys	missense	Exon 2 of 2	NP_001273270.1
	CBY2	NM_001286342.2		c.523G>A	p.Glu175Lys	missense	Exon 3 of 3	NP_001273271.1	Q8NA61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBY2	ENST00000310521.6	TSL:1 MANE Select	c.631G>A	p.Glu211Lys	missense	Exon 3 of 3	ENSP00000309189.1	Q8NA61-1
	CBY2	ENST00000378966.3	TSL:1	c.523G>A	p.Glu175Lys	missense	Exon 2 of 2	ENSP00000368249.3	Q8NA61-2
	CBY2	ENST00000610924.1	TSL:5	c.523G>A	p.Glu175Lys	missense	Exon 3 of 3	ENSP00000480148.1	Q8NA61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.078
Sift	Benign	0.086	T
Sift4G	Benign	0.57	T
Polyphen		0.63	P
Vest4		0.13
MutPred		0.23		Gain of ubiquitination at E211 (P = 0.0066)
MVP		0.35
MPC		0.57
ClinPred		0.41	T
GERP RS		4.6
Varity_R		0.088
gMVP		0.16
Mutation Taster		=94/6	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

hg19: chr13-46287791;