dbSNP rs12768019: CUL2:p.Lys32Lys (chr10-35100915-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000685421.1(CUL2):c.96A>G(p.Lys32Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,980 control chromosomes in the GnomAD database, including 7,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 7040 hom., cov: 31)

Exomes 𝑓: 0.40 ( 3 hom. )

Consequence

CUL2
ENST00000685421.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

Publications

12 publications found

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]

CUL2 links:

ENSG00000230534 (HGNC:):

ENSG00000230534 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000685421.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP7

Synonymous conserved (PhyloP=-2.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000685421.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CUL2	ENST00000685421.1	c.96A>G	p.Lys32Lys	synonymous	Exon 2 of 6	ENSP00000509605.1	A0A8I5KWB8
CUL2	ENST00000686156.1	c.96A>G	p.Lys32Lys	synonymous	Exon 2 of 6	ENSP00000509166.1	A0A8I5KWB8
CUL2	ENST00000688736.1	c.96A>G	p.Lys32Lys	synonymous	Exon 3 of 7	ENSP00000510643.1	A0A8I5KWB8

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44416

AN:

151794

Hom.:

7028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.162

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.316

GnomAD4 exome

AF:

0.397

AC:

AN:

Hom.:

Cov.:

AF XY:

0.413

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.414

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.293

AC:

44464

AN:

151912

Hom.:

7040

Cov.:

AF XY:

0.295

AC XY:

21913

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.163

AC:

6750

AN:

41490

American (AMR)

AF:

0.298

AC:

4534

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1385

AN:

3470

East Asian (EAS)

AF:

0.294

AC:

1514

AN:

5156

South Asian (SAS)

AF:

0.347

AC:

1667

AN:

4806

European-Finnish (FIN)

AF:

0.391

AC:

4113

AN:

10530

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23497

AN:

67938

Other (OTH)

AF:

0.323

AC:

681

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1547

3094

4640

6187

7734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.325

Hom.:

4554

Bravo

AF:

0.279

Asia WGS

AF:

0.342

AC:

1188

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.38

(source)

DANN

Benign

0.27

PhyloP100

-2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over