3-12810210-G-C

Variant names:

• chr3-12810210-G-C
• NM_001162499.2:c.643G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001162499.2(CAND2):​c.643G>C​(p.Ala215Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000719 in 1,390,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CAND2 NM_001162499.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.42

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND2	NM_001162499.2	c.643G>C	p.Ala215Pro	missense_variant	Exon 5 of 15	ENST00000456430.6	NP_001155971.1
CAND2	NM_012298.3	c.364G>C	p.Ala122Pro	missense_variant	Exon 3 of 13		NP_036430.1
CAND2	XM_011533504.3	c.571G>C	p.Ala191Pro	missense_variant	Exon 5 of 15		XP_011531806.1
CAND2	XM_011533503.3	c.643G>C	p.Ala215Pro	missense_variant	Exon 5 of 14		XP_011531805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAND2	ENST00000456430.6	c.643G>C	p.Ala215Pro	missense_variant	Exon 5 of 15	1	NM_001162499.2	ENSP00000387641.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1390502 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 686842

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.21
Sift	Benign	0.036	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.91	P;P
Vest4		0.63
MutPred		0.43		.;Gain of disorder (P = 0.0808);
MVP		0.92
MPC		2.2
ClinPred		0.80	D
GERP RS		4.0
Varity_R		0.63
gMVP		0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-12851709;