6-42603608-A-T

Variant names:

• chr6-42603608-A-T
• rs16895863
• NM_001363705.2:c.552A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001363705.2(UBR2):​c.552A>T​(p.Ser184Ser) 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
• Publications: 11 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 -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 rank	MANE	Protein	UniProt
UBR2	NM_001363705.2	c.552A>T	p.Ser184Ser	synonymous_variant	Exon 5 of 47	ENST00000372901.2	NP_001350634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBR2	ENST00000372901.2	c.552A>T	p.Ser184Ser	synonymous_variant	Exon 5 of 47	5	NM_001363705.2	ENSP00000361992.1
UBR2	ENST00000372899.6	c.552A>T	p.Ser184Ser	synonymous_variant	Exon 5 of 47	1		ENSP00000361990.1
UBR2	ENST00000372903.6	c.552A>T	p.Ser184Ser	synonymous_variant	Exon 5 of 12	1		ENSP00000361994.2
ENSG00000310435	ENST00000849798.1	n.298-2990T>A		intron_variant	Intron 1 of 1

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

GnomAD2 exomes AF: 0.200 AC: 42377 AN: 211544 AF XY: 0.204

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 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

African (AFR) AF: 0.240 AC: 7298 AN: 30426

American (AMR) AF: 0.174 AC: 5536 AN: 31820

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 4987 AN: 24844

East Asian (EAS) AF: 0.0783 AC: 2955 AN: 37734

South Asian (SAS) AF: 0.231 AC: 18055 AN: 78118

European-Finnish (FIN) AF: 0.200 AC: 10523 AN: 52656

Middle Eastern (MID) AF: 0.238 AC: 1341 AN: 5626

European-Non Finnish (NFE) AF: 0.208 AC: 228317 AN: 1099474

Other (OTH) AF: 0.210 AC: 12295 AN: 58584

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

African (AFR) AF: 0.239 AC: 9878 AN: 41370

American (AMR) AF: 0.187 AC: 2847 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.109 AC: 563 AN: 5166

South Asian (SAS) AF: 0.232 AC: 1115 AN: 4810

European-Finnish (FIN) AF: 0.201 AC: 2105 AN: 10498

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14442 AN: 67898

Other (OTH) AF: 0.219 AC: 462 AN: 2110

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
PhyloP100		0.081
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs16895863; hg19: chr6-42571346; COSMIC: COSV65768691;