chr10-35044652-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003591.4(CUL2):​c.628C>T​(p.Pro210Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000683 in 1,609,386 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CUL2
NM_003591.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.72
Variant links:
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.4158293).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CUL2NM_003591.4 linkuse as main transcriptc.628C>T p.Pro210Ser missense_variant 8/21 ENST00000374749.8 NP_003582.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CUL2ENST00000374749.8 linkuse as main transcriptc.628C>T p.Pro210Ser missense_variant 8/211 NM_003591.4 ENSP00000363881 P3Q13617-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152152
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000412
AC:
6
AN:
1457234
Hom.:
0
Cov.:
30
AF XY:
0.00000414
AC XY:
3
AN XY:
724728
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000506
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152152
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74324
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:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
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 submitterclinical testingAmbry GeneticsApr 25, 2023The c.685C>T (p.P229S) alteration is located in exon 8 (coding exon 8) of the CUL2 gene. This alteration results from a C to T substitution at nucleotide position 685, causing the proline (P) at amino acid position 229 to be replaced by a serine (S). 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
0.17
BayesDel_addAF
Benign
-0.012
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.78
.;D;D;D;.;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
.;.;.;D;D;D;D
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.42
T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.032
T
MutationAssessor
Benign
1.8
.;L;L;L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-5.1
D;D;D;D;.;.;.
REVEL
Uncertain
0.46
Sift
Uncertain
0.014
D;D;D;D;.;.;.
Sift4G
Benign
0.28
T;T;T;T;T;T;T
Polyphen
0.96
D;B;B;B;.;D;.
Vest4
0.28
MVP
0.67
MPC
0.81
ClinPred
0.94
D
GERP RS
4.8
Varity_R
0.57
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs377244893; hg19: chr10-35333580; API