chr10-35011943-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003591.4(CUL2):c.2011G>T(p.Ala671Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,605,022 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
CUL2
NM_003591.4 missense
NM_003591.4 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 7.90
Genes affected
CUL2 (HGNC:2552): (cullin 2) Enables ubiquitin protein ligase binding activity. Predicted to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Predicted to act upstream of or within protein catabolic process. Located in nucleoplasm. Part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL2 | NM_003591.4 | c.2011G>T | p.Ala671Ser | missense_variant | 20/21 | ENST00000374749.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL2 | ENST00000374749.8 | c.2011G>T | p.Ala671Ser | missense_variant | 20/21 | 1 | NM_003591.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
1
AN:
152076
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1452946Hom.: 0 Cov.: 29 AF XY: 0.00000415 AC XY: 3AN XY: 722482
GnomAD4 exome
AF:
AC:
3
AN:
1452946
Hom.:
Cov.:
29
AF XY:
AC XY:
3
AN XY:
722482
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74266
GnomAD4 genome
?
AF:
AC:
1
AN:
152076
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74266
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2023 | The c.2068G>T (p.A690S) alteration is located in exon 20 (coding exon 20) of the CUL2 gene. This alteration results from a G to T substitution at nucleotide position 2068, causing the alanine (A) at amino acid position 690 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.;.
REVEL
Uncertain
Sift
Benign
T;T;T;.;.
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;.;.
Vest4
MutPred
Gain of phosphorylation at A671 (P = 0.0081);Gain of phosphorylation at A671 (P = 0.0081);Gain of phosphorylation at A671 (P = 0.0081);.;.;
MVP
MPC
1.8
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at