rs549612663

Variant names:

• chr3-12807379-C-G
• rs549612663
• NM_001162499.2:c.286C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-12807379-C-G
• chr3-12807379-C-T

Variant summary

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

The NM_001162499.2(CAND2):​c.286C>G​(p.Arg96Gly) 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. 13/22 in silico tools predict 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. R96Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAND2 NM_001162499.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 0 publications found

Genes affected

CAND2 (HGNC:30689): (cullin associated and neddylation dissociated 2 (putative)) Predicted to enable TBP-class protein binding activity. Predicted to be involved in SCF complex assembly; positive regulation of transcription, DNA-templated; and protein ubiquitination. Located in cytosol. [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=0.11745629).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162499.2. 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
	CAND2	NM_001162499.2	MANE Select	c.286C>G	p.Arg96Gly	missense	Exon 3 of 15	NP_001155971.1	O75155-1
	CAND2	NM_012298.3		c.213-2680C>G		intron	N/A	NP_036430.1	O75155-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAND2	ENST00000456430.6	TSL:1 MANE Select	c.286C>G	p.Arg96Gly	missense	Exon 3 of 15	ENSP00000387641.2	O75155-1
	CAND2	ENST00000295989.9	TSL:1	c.213-2680C>G		intron	N/A	ENSP00000295989.5	O75155-2
	CAND2	ENST00000949513.1		c.286C>G	p.Arg96Gly	missense	Exon 3 of 14	ENSP00000619572.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.045
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.14	N
PhyloP100		1.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.072
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.038	D
Polyphen		0.0020	B
Vest4		0.25
MutPred		0.39		Loss of stability (P = 0.1137)
MVP		0.26
MPC		1.5
ClinPred		0.74	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.14
Mutation Taster		=78/22	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: rs549612663; hg19: chr3-12848878;