chr3-12807362-C-T

Variant summary

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

The NM_001162499.2(CAND2):​c.269C>T​(p.Thr90Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000416 in 1,551,748 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 0.00041 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

CAND2
NM_001162499.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05
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=0.034095973).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAND2NM_001162499.2 linkc.269C>T p.Thr90Ile missense_variant Exon 3 of 15 ENST00000456430.6 NP_001155971.1 O75155-1
CAND2XM_011533504.3 linkc.197C>T p.Thr66Ile missense_variant Exon 3 of 15 XP_011531806.1
CAND2XM_011533503.3 linkc.269C>T p.Thr90Ile missense_variant Exon 3 of 14 XP_011531805.1
CAND2NM_012298.3 linkc.213-2697C>T intron_variant Intron 2 of 12 NP_036430.1 O75155-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAND2ENST00000456430.6 linkc.269C>T p.Thr90Ile missense_variant Exon 3 of 15 1 NM_001162499.2 ENSP00000387641.2 O75155-1

Frequencies

GnomAD3 genomes
AF:
0.000407
AC:
62
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00137
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000412
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000536
AC:
84
AN:
156690
Hom.:
0
AF XY:
0.000494
AC XY:
41
AN XY:
82990
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00158
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00101
Gnomad NFE exome
AF:
0.000412
Gnomad OTH exome
AF:
0.000682
GnomAD4 exome
AF:
0.000417
AC:
584
AN:
1399426
Hom.:
0
Cov.:
34
AF XY:
0.000406
AC XY:
280
AN XY:
690216
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.00148
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000280
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000771
Gnomad4 NFE exome
AF:
0.000430
Gnomad4 OTH exome
AF:
0.000465
GnomAD4 genome
AF:
0.000407
AC:
62
AN:
152322
Hom.:
0
Cov.:
33
AF XY:
0.000483
AC XY:
36
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000304
Hom.:
0
Bravo
AF:
0.000472
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000723
AC:
1
ESP6500EA
AF:
0.000629
AC:
2
ExAC
AF:
0.000228
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.269C>T (p.T90I) alteration is located in exon 3 (coding exon 3) of the CAND2 gene. This alteration results from a C to T substitution at nucleotide position 269, causing the threonine (T) at amino acid position 90 to be replaced by an isoleucine (I). 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
0.13
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.078
T
Eigen
Benign
-0.065
Eigen_PC
Benign
0.053
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.034
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-3.2
D
REVEL
Benign
0.10
Sift
Benign
0.051
T
Sift4G
Benign
0.14
T
Polyphen
0.0030
B
Vest4
0.27
MVP
0.35
MPC
1.2
ClinPred
0.058
T
GERP RS
4.6
Varity_R
0.17
gMVP
0.11

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.

Other links and lift over

dbSNP: rs187232301; hg19: chr3-12848861; API