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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 2653547.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND2	NM_001162499.2 link	c.992A>T	p.Glu331Val	missense_variant	Exon 7 of 15	ENST00000456430.6	NP_001155971.1	O75155-1
CAND2	NM_012298.3 link	c.713A>T	p.Glu238Val	missense_variant	Exon 5 of 13		NP_036430.1	O75155-2
CAND2	XM_011533504.3 link	c.920A>T	p.Glu307Val	missense_variant	Exon 7 of 15		XP_011531806.1
CAND2	XM_011533503.3 link	c.992A>T	p.Glu331Val	missense_variant	Exon 7 of 14		XP_011531805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CAND2	ENST00000456430.6 link	c.992A>T	p.Glu331Val	missense_variant	Exon 7 of 15	1	NM_001162499.2	ENSP00000387641.2	O75155-1
CAND2	ENST00000295989.9 link	c.713A>T	p.Glu238Val	missense_variant	Exon 5 of 13	1		ENSP00000295989.5	O75155-2
CAND2	ENST00000650119.1 link	n.*830A>T		non_coding_transcript_exon_variant	Exon 8 of 16			ENSP00000497240.1	A0A3B3ISC4
CAND2	ENST00000650119.1 link	n.*830A>T		3_prime_UTR_variant	Exon 8 of 16			ENSP00000497240.1	A0A3B3ISC4

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

GnomAD3 exomes

AF:

0.00559

AC:

1390

AN:

248814

Hom.:

AF XY:

0.00581

AC XY:

785

AN XY:

135000

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 SAS exome

AF:

0.00246

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

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00586

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00234

Gnomad4 FIN exome

AF:

0.00318

Gnomad4 NFE exome

AF:

0.00660

Gnomad4 OTH exome

AF:

0.00725

GnomAD4 genome

AF:

0.00527

AC:

803

AN:

152308

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

359

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00771

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00764

Gnomad4 OTH

AF:

0.00804

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CAND2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.38

B;B

Vest4

0.45

MVP

0.85

MPC

0.52

ClinPred

0.047

GERP RS

4.7

Varity_R

0.41

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over