rs7099036

chr10-35060646-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003591.4(CUL2):c.317+228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,028 control chromosomes in the GnomAD database, including 8,637 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 (8637 hom., cov: 32)
• Consequence: CUL2 NM_003591.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL2	NM_003591.4	c.317+228G>A		intron_variant		ENST00000374749.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL2	ENST00000374749.8	c.317+228G>A		intron_variant		1	NM_003591.4	P3

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51066 AN: 151910 Hom.: 8613 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.336 AC: 51145 AN: 152028 Hom.: 8637 Cov.: 32 AF XY: 0.337 AC XY: 25077 AN XY: 74314

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.351

Alfa AF: 0.344 Hom.: 9593

Bravo AF: 0.328

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.45
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs7099036; hg19: chr10-35349574; COSMIC: COSV66081422; COSMIC: COSV66081422;