3-12810078-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001162499.2(CAND2):​c.511G>A​(p.Ala171Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,438,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

CAND2
NM_001162499.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.063529074).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAND2NM_001162499.2 linkc.511G>A p.Ala171Thr missense_variant Exon 5 of 15 ENST00000456430.6 NP_001155971.1 O75155-1
CAND2NM_012298.3 linkc.232G>A p.Ala78Thr missense_variant Exon 3 of 13 NP_036430.1 O75155-2
CAND2XM_011533504.3 linkc.439G>A p.Ala147Thr missense_variant Exon 5 of 15 XP_011531806.1
CAND2XM_011533503.3 linkc.511G>A p.Ala171Thr missense_variant Exon 5 of 14 XP_011531805.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAND2ENST00000456430.6 linkc.511G>A p.Ala171Thr missense_variant Exon 5 of 15 1 NM_001162499.2 ENSP00000387641.2 O75155-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000156
AC:
2
AN:
1285978
Hom.:
0
Cov.:
31
AF XY:
0.00000160
AC XY:
1
AN XY:
625462
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.72e-7
Gnomad4 OTH exome
AF:
0.0000187
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000897
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.511G>A (p.A171T) alteration is located in exon 5 (coding exon 5) of the CAND2 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the alanine (A) at amino acid position 171 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
20
DANN
Benign
0.93
DEOGEN2
Benign
0.0047
.;T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.064
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.090
.;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.070
N;N
REVEL
Benign
0.033
Sift
Benign
0.78
T;T
Sift4G
Benign
0.39
T;T
Polyphen
0.0
B;B
Vest4
0.044
MutPred
0.42
.;Loss of catalytic residue at G166 (P = 0.3081);
MVP
0.63
MPC
1.1
ClinPred
0.18
T
GERP RS
0.30
Varity_R
0.037
gMVP
0.086

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs746747163; hg19: chr3-12851577; API