6-42603608-A-T

Position:

• chr6-42603608-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001363705.2(UBR2):​c.552A>T​(p.Ser184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,571,060 control chromosomes in the GnomAD database, including 34,413 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 0.21 (3473 hom., cov: 31)
  • Exomes 𝑓: 0.21 (30940 hom.)
• Consequence: UBR2 NM_001363705.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.081 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.552A>T	p.Ser184=	synonymous_variant	5/47	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.552A>T	p.Ser184=	synonymous_variant	5/47	5	NM_001363705.2	ENSP00000361992	P3
UBR2	ENST00000372899.6	c.552A>T	p.Ser184=	synonymous_variant	5/47	1		ENSP00000361990	A1
UBR2	ENST00000372903.6	c.552A>T	p.Ser184=	synonymous_variant	5/12	1		ENSP00000361994

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32267 AN: 151660 Hom.: 3465 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.200 AC: 42377 AN: 211544 Hom.: 4497 AF XY: 0.204 AC XY: 23582 AN XY: 115834

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.103

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.209

GnomAD4 exome AF: 0.205 AC: 291307 AN: 1419282 Hom.: 30940 Cov.: 31 AF XY: 0.206 AC XY: 145681 AN XY: 706040

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.0783

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.213 AC: 32297 AN: 151778 Hom.: 3473 Cov.: 31 AF XY: 0.211 AC XY: 15624 AN XY: 74164

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.219

Alfa AF: 0.181 Hom.: 936

Bravo AF: 0.211

Asia WGS AF: 0.204 AC: 707 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.7
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs16895863; hg19: chr6-42571346; COSMIC: COSV65768691;