NM_001363705.2:c.663A>G

Variant names:

• chr6-42605721-A-G
• rs1005527200
• NM_001363705.2:c.663A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001363705.2(UBR2):​c.663A>G​(p.Val221Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UBR2 NM_001363705.2 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003922
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 6-42605721-A-G is Benign according to our data. Variant chr6-42605721-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2656554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.18 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR2	NM_001363705.2	MANE Select	c.663A>G	p.Val221Val	splice_region synonymous	Exon 6 of 47	NP_001350634.1	Q8IWV8-4
	UBR2	NM_015255.3		c.663A>G	p.Val221Val	splice_region synonymous	Exon 6 of 47	NP_056070.1	Q8IWV8-1
	UBR2	NM_001184801.2		c.663A>G	p.Val221Val	splice_region synonymous	Exon 6 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.663A>G	p.Val221Val	splice_region synonymous	Exon 6 of 47	ENSP00000361992.1	Q8IWV8-4
	UBR2	ENST00000372899.6	TSL:1	c.663A>G	p.Val221Val	splice_region synonymous	Exon 6 of 47	ENSP00000361990.1	Q8IWV8-1
	UBR2	ENST00000372903.6	TSL:1	c.663A>G	p.Val221Val	splice_region synonymous	Exon 6 of 12	ENSP00000361994.2	Q8IWV8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1444046 Hom.: 0 Cov.: 30 AF XY: 0.00000279 AC XY: 2 AN XY: 717948

African (AFR) AF: 0.00 AC: 0 AN: 32344

American (AMR) AF: 0.00 AC: 0 AN: 39696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25236

East Asian (EAS) AF: 0.00 AC: 0 AN: 39572

South Asian (SAS) AF: 0.00 AC: 0 AN: 82012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52690

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5680

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107182

Other (OTH) AF: 0.00 AC: 0 AN: 59634

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	8.5
DANN	Benign	0.85
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.0020
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: rs1005527200; hg19: chr6-42573459;