10-35017061-C-G

Variant names:

• chr10-35017061-C-G
• rs12268745
• NM_003591.4:c.1685-667G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003591.4(CUL2):​c.1685-667G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,720 control chromosomes in the GnomAD database, including 8,682 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 0.34 (8682 hom., cov: 31)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 6 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL2	NM_003591.4	c.1685-667G>C		intron_variant	Intron 17 of 20	ENST00000374749.8	NP_003582.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL2	ENST00000374749.8	c.1685-667G>C		intron_variant	Intron 17 of 20	1	NM_003591.4	ENSP00000363881.3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51169 AN: 151602 Hom.: 8659 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51247 AN: 151720 Hom.: 8682 Cov.: 31 AF XY: 0.339 AC XY: 25105 AN XY: 74122

African (AFR) AF: 0.318 AC: 13132 AN: 41320

American (AMR) AF: 0.314 AC: 4788 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1525 AN: 5144

South Asian (SAS) AF: 0.347 AC: 1668 AN: 4808

European-Finnish (FIN) AF: 0.392 AC: 4105 AN: 10480

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23576 AN: 67934

Other (OTH) AF: 0.349 AC: 737 AN: 2114

Alfa AF: 0.327 Hom.: 1016

Bravo AF: 0.329

Asia WGS AF: 0.352 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.35
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12268745; hg19: chr10-35305989;