dbSNP rs745574996: CAND2:p.Pro74Leu (chr3-12807314-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001162499.2(CAND2):c.221C>T(p.Pro74Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000709 in 1,551,238 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 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CAND2
NM_001162499.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Publications

0 publications found

Variant links:

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]

CAND2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.22126377).

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.221C>T	p.Pro74Leu	missense	Exon 3 of 15	NP_001155971.1	O75155-1
	CAND2	NM_012298.3		c.213-2745C>T		intron	N/A	NP_036430.1	O75155-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAND2	ENST00000456430.6	TSL:1 MANE Select	c.221C>T	p.Pro74Leu	missense	Exon 3 of 15	ENSP00000387641.2	O75155-1
CAND2	ENST00000295989.9	TSL:1	c.213-2745C>T		intron	N/A	ENSP00000295989.5	O75155-2
CAND2	ENST00000949513.1		c.221C>T	p.Pro74Leu	missense	Exon 3 of 14	ENSP00000619572.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000641

AC:

AN:

155942

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000126

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000357

AC:

AN:

1399104

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690058

show subpopulations

African (AFR)

AF:

0.0000633

AC:

AN:

31594

American (AMR)

AF:

0.00

AC:

AN:

35688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25144

East Asian (EAS)

AF:

0.00

AC:

AN:

35730

South Asian (SAS)

AF:

0.00

AC:

AN:

79202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078782

Other (OTH)

AF:

0.00

AC:

AN:

57994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000381

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

Eigen

Benign

0.091

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.032

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

6.0

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-7.2

REVEL

Benign

0.18

Sift

Benign

0.089

Sift4G

Benign

0.15

Polyphen

0.012

Vest4

0.44

MutPred

0.46

Gain of ubiquitination at K78 (P = 0.1418)

MVP

0.39

MPC

1.9

ClinPred

0.64

GERP RS

4.8

Varity_R

0.34

gMVP

0.52

Mutation Taster

=64/36

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over