Genetic Variant CAND2:p.Glu331Val (chr3-12813374-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001162499.2(CAND2):c.992A>T(p.Glu331Val) variant causes a missense change. The variant allele was found at a frequency of 0.00601 in 1,613,728 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 40 hom. )

Consequence

CAND2
NM_001162499.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.31

Publications

13 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043477714).

BP6

Variant 3-12813374-A-T is Benign according to our data. Variant chr3-12813374-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2653547.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 40 AR gene

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.992A>T	p.Glu331Val	missense	Exon 7 of 15	NP_001155971.1	O75155-1
	CAND2	NM_012298.3		c.713A>T	p.Glu238Val	missense	Exon 5 of 13	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.992A>T	p.Glu331Val	missense	Exon 7 of 15	ENSP00000387641.2	O75155-1
CAND2	ENST00000295989.9	TSL:1	c.713A>T	p.Glu238Val	missense	Exon 5 of 13	ENSP00000295989.5	O75155-2
CAND2	ENST00000856238.1		c.713A>T	p.Glu238Val	missense	Exon 5 of 13	ENSP00000526297.1

Frequencies

GnomAD3 genomes

AF:

0.00527

AC:

802

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00764

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00559

AC:

1390

AN:

248814

AF XY:

0.00581

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00595

Gnomad ASJ exome

AF:

0.0132

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00293

Gnomad NFE exome

AF:

0.00736

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00609

AC:

8893

AN:

1461420

Hom.:

Cov.:

AF XY:

0.00607

AC XY:

4413

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

33468

American (AMR)

AF:

0.00586

AC:

262

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

378

AN:

26116

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00234

AC:

202

AN:

86192

European-Finnish (FIN)

AF:

0.00318

AC:

170

AN:

53402

Middle Eastern (MID)

AF:

0.0112

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00660

AC:

7336

AN:

1111790

Other (OTH)

AF:

0.00725

AC:

438

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

433

866

1300

1733

2166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.00527

AC:

803

AN:

152308

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41558

American (AMR)

AF:

0.00771

AC:

118

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00331

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00764

AC:

520

AN:

68020

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00744

Hom.:

Bravo

AF:

0.00543

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000949

AC:

ESP6500EA

AF:

0.00816

AC:

ExAC

AF:

0.00487

AC:

590

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00818

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.6

PhyloP100

5.3

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.23

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

0.38

Vest4

0.45

MVP

0.85

MPC

0.52

ClinPred

0.047

GERP RS

4.7

Varity_R

0.41

gMVP

0.43

Mutation Taster

=86/14

polymorphism

(source)

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

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