dbSNP rs140295185: CAND2:p.Ala215Thr (chr3-12810210-G-A) – 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.643G>A(p.Ala215Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00511 in 1,542,864 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 34 hom. )

Consequence

CAND2
NM_001162499.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.42

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=0.003944695).

BP6

Variant 3-12810210-G-A is Benign according to our data. Variant chr3-12810210-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653546.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAND2	NM_001162499.2 link	c.643G>A	p.Ala215Thr	missense_variant	Exon 5 of 15	ENST00000456430.6	NP_001155971.1	O75155-1
CAND2	NM_012298.3 link	c.364G>A	p.Ala122Thr	missense_variant	Exon 3 of 13		NP_036430.1	O75155-2
CAND2	XM_011533504.3 link	c.571G>A	p.Ala191Thr	missense_variant	Exon 5 of 15		XP_011531806.1
CAND2	XM_011533503.3 link	c.643G>A	p.Ala215Thr	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 link	c.643G>A	p.Ala215Thr	missense_variant	Exon 5 of 15	1	NM_001162499.2	ENSP00000387641.2		O75155-1

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

751

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00586

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00440

AC:

607

AN:

137872

Hom.:

AF XY:

0.00416

AC XY:

318

AN XY:

76436

show subpopulations

Gnomad AFR exome

AF:

0.00230

Gnomad AMR exome

AF:

0.000440

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000367

Gnomad FIN exome

AF:

0.0221

Gnomad NFE exome

AF:

0.00631

Gnomad OTH exome

AF:

0.00254

GnomAD4 exome

AF:

0.00513

AC:

7129

AN:

1390496

Hom.:

Cov.:

AF XY:

0.00494

AC XY:

3394

AN XY:

686840

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.000462

Gnomad4 ASJ exome

AF:

0.000121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000458

Gnomad4 FIN exome

AF:

0.0218

Gnomad4 NFE exome

AF:

0.00550

Gnomad4 OTH exome

AF:

0.00320

GnomAD4 genome

AF:

0.00493

AC:

751

AN:

152368

Hom.:

Cov.:

AF XY:

0.00550

AC XY:

410

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0226

Gnomad4 NFE

AF:

0.00587

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00410

Hom.:

Bravo

AF:

0.00302

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00151

AC:

ESP6500EA

AF:

0.00379

AC:

ExAC

AF:

0.00349

AC:

389

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CAND2: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0072

.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.84

T;D

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

.;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.28

N;N

REVEL

Benign

0.13

Sift

Benign

0.78

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.017

B;B

Vest4

0.18

MVP

0.74

MPC

1.1

ClinPred

0.070

GERP RS

4.0

Varity_R

0.091

gMVP

0.14

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