NM_001162499.2:c.754C>G

Variant names:

• chr3-12810321-C-G
• rs2061841634
• NM_001162499.2:c.754C>G

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.754C>G​(p.Leu252Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,304,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CAND2 NM_001162499.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• 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=0.10482606).

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.754C>G	p.Leu252Val	missense	Exon 5 of 15	NP_001155971.1	O75155-1
	CAND2	NM_012298.3		c.475C>G	p.Leu159Val	missense	Exon 3 of 13	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.754C>G	p.Leu252Val	missense	Exon 5 of 15	ENSP00000387641.2	O75155-1
	CAND2	ENST00000295989.9	TSL:1	c.475C>G	p.Leu159Val	missense	Exon 3 of 13	ENSP00000295989.5	O75155-2
	CAND2	ENST00000856238.1		c.475C>G	p.Leu159Val	missense	Exon 3 of 13	ENSP00000526297.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1304234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 636030

African (AFR) AF: 0.00 AC: 0 AN: 26674

American (AMR) AF: 0.0000391 AC: 1 AN: 25562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20302

East Asian (EAS) AF: 0.00 AC: 0 AN: 31598

South Asian (SAS) AF: 0.00 AC: 0 AN: 67130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3930

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1036908

Other (OTH) AF: 0.00 AC: 0 AN: 53810

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.0089	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.14	N
PhyloP100		1.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.049
Sift	Benign	0.37	T
Sift4G	Benign	0.74	T
Polyphen		0.0070	B
Vest4		0.17
MutPred		0.47		Gain of MoRF binding (P = 0.0951)
MVP		0.39
MPC		1.1
ClinPred		0.16	T
GERP RS		4.2
Varity_R		0.074
gMVP		0.23
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2061841634; hg19: chr3-12851820;