NM_001363705.2:c.818G>A

Variant names:

• chr6-42606605-G-A
• rs752489829
• NM_001363705.2:c.818G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001363705.2(UBR2):​c.818G>A​(p.Arg273Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,457,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: UBR2 NM_001363705.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3449791).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363705.2. 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
	UBR2	NM_001363705.2	MANE Select	c.818G>A	p.Arg273Gln	missense	Exon 7 of 47	NP_001350634.1	Q8IWV8-4
	UBR2	NM_015255.3		c.818G>A	p.Arg273Gln	missense	Exon 7 of 47	NP_056070.1	Q8IWV8-1
	UBR2	NM_001184801.2		c.818G>A	p.Arg273Gln	missense	Exon 7 of 12	NP_001171730.1	Q8IWV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	ENST00000372901.2	TSL:5 MANE Select	c.818G>A	p.Arg273Gln	missense	Exon 7 of 47	ENSP00000361992.1	Q8IWV8-4
	UBR2	ENST00000372899.6	TSL:1	c.818G>A	p.Arg273Gln	missense	Exon 7 of 47	ENSP00000361990.1	Q8IWV8-1
	UBR2	ENST00000372903.6	TSL:1	c.818G>A	p.Arg273Gln	missense	Exon 7 of 12	ENSP00000361994.2	Q8IWV8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000363 AC: 9 AN: 247884 AF XY: 0.0000448

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000117 AC: 17 AN: 1457176 Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 10 AN XY: 724708

African (AFR) AF: 0.00 AC: 0 AN: 33324

American (AMR) AF: 0.0000227 AC: 1 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.000178 AC: 7 AN: 39334

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5744

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110324

Other (OTH) AF: 0.0000166 AC: 1 AN: 60214

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.24
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.026	D
Polyphen		0.99	D
Vest4		0.52
MutPred		0.56		Loss of MoRF binding (P = 0.0262)
MVP		0.53
MPC		1.3
ClinPred		0.28	T
GERP RS		4.6
Varity_R		0.36
gMVP		0.73
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs752489829; hg19: chr6-42574343;