6-42600510-T-C

Variant names:

• chr6-42600510-T-C
• rs2025249
• NM_001363705.2:c.532-3078T>C

Variant summary

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

The NM_001363705.2(UBR2):​c.532-3078T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 151,754 control chromosomes in the GnomAD database, including 43,433 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 0.75 (43433 hom., cov: 29)
• Consequence: UBR2 NM_001363705.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 6 publications found

Genes affected

UBR2 (HGNC:21289): (ubiquitin protein ligase E3 component n-recognin 2) Enables leucine binding activity. Involved in cellular response to leucine and negative regulation of TOR signaling. Predicted to be located in cytosol. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. Predicted to colocalize with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000310435 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.532-3078T>C		intron_variant	Intron 4 of 46	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.532-3078T>C		intron_variant	Intron 4 of 46	5	NM_001363705.2	ENSP00000361992.1
UBR2	ENST00000372899.6	c.532-3078T>C		intron_variant	Intron 4 of 46	1		ENSP00000361990.1
UBR2	ENST00000372903.6	c.532-3078T>C		intron_variant	Intron 4 of 11	1		ENSP00000361994.2
ENSG00000310435	ENST00000849798.1	n.406A>G		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114170 AN: 151638 Hom.: 43384 Cov.: 29

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.753 AC: 114279 AN: 151754 Hom.: 43433 Cov.: 29 AF XY: 0.752 AC XY: 55760 AN XY: 74134

African (AFR) AF: 0.852 AC: 35221 AN: 41360

American (AMR) AF: 0.691 AC: 10509 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3470

East Asian (EAS) AF: 0.543 AC: 2804 AN: 5168

South Asian (SAS) AF: 0.782 AC: 3760 AN: 4810

European-Finnish (FIN) AF: 0.754 AC: 7903 AN: 10486

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49196 AN: 67940

Other (OTH) AF: 0.755 AC: 1591 AN: 2106

Alfa AF: 0.742 Hom.: 7350

Bravo AF: 0.746

Asia WGS AF: 0.698 AC: 2425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		0.012
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: rs2025249; hg19: chr6-42568248; COSMIC: COSV65767649;