10-35049676-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003591.4(CUL2):​c.506+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00807 in 1,607,258 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0082 ( 85 hom. )

Consequence

CUL2
NM_003591.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00006623
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.00
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 10-35049676-C-G is Benign according to our data. Variant chr10-35049676-C-G is described in ClinVar as [Benign]. Clinvar id is 708941.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 996 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CUL2NM_003591.4 linkuse as main transcriptc.506+7G>C splice_region_variant, intron_variant ENST00000374749.8 NP_003582.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CUL2ENST00000374749.8 linkuse as main transcriptc.506+7G>C splice_region_variant, intron_variant 1 NM_003591.4 ENSP00000363881 P3Q13617-1

Frequencies

GnomAD3 genomes
AF:
0.00655
AC:
996
AN:
152096
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00106
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00346
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0343
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00798
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.00691
AC:
1724
AN:
249468
Hom.:
12
AF XY:
0.00677
AC XY:
912
AN XY:
134794
show subpopulations
Gnomad AFR exome
AF:
0.00170
Gnomad AMR exome
AF:
0.00134
Gnomad ASJ exome
AF:
0.00271
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000992
Gnomad FIN exome
AF:
0.0329
Gnomad NFE exome
AF:
0.00754
Gnomad OTH exome
AF:
0.00951
GnomAD4 exome
AF:
0.00823
AC:
11979
AN:
1455044
Hom.:
85
Cov.:
29
AF XY:
0.00803
AC XY:
5812
AN XY:
724098
show subpopulations
Gnomad4 AFR exome
AF:
0.00135
Gnomad4 AMR exome
AF:
0.00155
Gnomad4 ASJ exome
AF:
0.00246
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000175
Gnomad4 FIN exome
AF:
0.0330
Gnomad4 NFE exome
AF:
0.00871
Gnomad4 OTH exome
AF:
0.00640
GnomAD4 genome
AF:
0.00654
AC:
996
AN:
152214
Hom.:
8
Cov.:
32
AF XY:
0.00738
AC XY:
549
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00106
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00346
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0343
Gnomad4 NFE
AF:
0.00798
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00706
Hom.:
2
Bravo
AF:
0.00427
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
1.2
DANN
Benign
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000066
dbscSNV1_RF
Benign
0.0
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: rs145366778; hg19: chr10-35338604; API