13-45713269-C-A

Variant names:

• chr13-45713269-C-A
• rs372471800
• NM_152719.3:c.244C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152719.3(CBY2):​c.244C>A​(p.Arg82Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBY2 NM_152719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3558519).

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.244C>A	p.Arg82Ser	missense	Exon 3 of 3	NP_689932.1	Q8NA61-1
	CBY2	NM_001286341.2		c.163C>A	p.Arg55Ser	missense	Exon 2 of 2	NP_001273270.1
	CBY2	NM_001286342.2		c.136C>A	p.Arg46Ser	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.244C>A	p.Arg82Ser	missense	Exon 3 of 3	ENSP00000309189.1	Q8NA61-1
	CBY2	ENST00000378966.3	TSL:1	c.136C>A	p.Arg46Ser	missense	Exon 2 of 2	ENSP00000368249.3	Q8NA61-2
	CBY2	ENST00000610924.1	TSL:5	c.136C>A	p.Arg46Ser	missense	Exon 3 of 3	ENSP00000480148.1	Q8NA61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249458 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: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.0070	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.44
MVP		0.71
MPC		0.69
ClinPred		0.80	D
GERP RS		5.1
Varity_R		0.26
gMVP		0.44
Mutation Taster		=77/23	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

dbSNP: rs372471800; hg19: chr13-46287404;