6-42603608-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001363705.2(UBR2):​c.552A>G​(p.Ser184Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,420,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.081 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	NM_001363705.2	MANE Select	c.552A>G	p.Ser184Ser	synonymous	Exon 5 of 47	NP_001350634.1
	UBR2	NM_015255.3		c.552A>G	p.Ser184Ser	synonymous	Exon 5 of 47	NP_056070.1
	UBR2	NM_001184801.2		c.552A>G	p.Ser184Ser	synonymous	Exon 5 of 12	NP_001171730.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	ENST00000372901.2	TSL:5 MANE Select	c.552A>G	p.Ser184Ser	synonymous	Exon 5 of 47	ENSP00000361992.1
	UBR2	ENST00000372899.6	TSL:1	c.552A>G	p.Ser184Ser	synonymous	Exon 5 of 47	ENSP00000361990.1
	UBR2	ENST00000372903.6	TSL:1	c.552A>G	p.Ser184Ser	synonymous	Exon 5 of 12	ENSP00000361994.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000282 AC: 4 AN: 1420826 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 706734

African (AFR) AF: 0.00 AC: 0 AN: 30472

American (AMR) AF: 0.00 AC: 0 AN: 31862

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24860

East Asian (EAS) AF: 0.00 AC: 0 AN: 37754

South Asian (SAS) AF: 0.00 AC: 0 AN: 78202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1100696

Other (OTH) AF: 0.00 AC: 0 AN: 58654

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 936

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.2
DANN	Benign	0.71
PhyloP100		0.081

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;