chr3-12807362-C-T

Variant names:

• chr3-12807362-C-T
• rs187232301
• NM_001162499.2:c.269C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001162499.2(CAND2):​c.269C>T​(p.Thr90Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000416 in 1,551,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (0 hom.)
• Consequence: CAND2 NM_001162499.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034095973).

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.269C>T	p.Thr90Ile	missense	Exon 3 of 15	NP_001155971.1	O75155-1
	CAND2	NM_012298.3		c.213-2697C>T		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.269C>T	p.Thr90Ile	missense	Exon 3 of 15	ENSP00000387641.2	O75155-1
	CAND2	ENST00000295989.9	TSL:1	c.213-2697C>T		intron	N/A	ENSP00000295989.5	O75155-2
	CAND2	ENST00000949513.1		c.269C>T	p.Thr90Ile	missense	Exon 3 of 14	ENSP00000619572.1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000536 AC: 84 AN: 156690 AF XY: 0.000494

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00101

Gnomad NFE exome AF: 0.000412

Gnomad OTH exome AF: 0.000682

GnomAD4 exome AF: 0.000417 AC: 584 AN: 1399426 Hom.: 0 Cov.: 34 AF XY: 0.000406 AC XY: 280 AN XY: 690216

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.00148 AC: 53 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.000771 AC: 38 AN: 49300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000430 AC: 464 AN: 1078956

Other (OTH) AF: 0.000465 AC: 27 AN: 58016

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.000483 AC XY: 36 AN XY: 74488

African (AFR) AF: 0.000144 AC: 6 AN: 41566

American (AMR) AF: 0.00137 AC: 21 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000367 Hom.: 0

Bravo AF: 0.000472

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.000629 AC: 2

ExAC AF: 0.000228 AC: 6

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	0.13
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.053
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		6.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.10
Sift	Benign	0.051	T
Sift4G	Benign	0.14	T
Polyphen		0.0030	B
Vest4		0.27
MVP		0.35
MPC		1.2
ClinPred		0.058	T
GERP RS		4.6
Varity_R		0.17
gMVP		0.11
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: rs187232301; hg19: chr3-12848861; COSMIC: COSV106094534;