2-237973180-G-T

Variant names:

• chr2-237973180-G-T
• rs968464715
• NM_080678.3:c.73G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080678.3(UBE2F):​c.73G>T​(p.Asp25Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,746 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D25N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UBE2F NM_080678.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98
• Publications: 0 publications found

Genes affected

UBE2F (HGNC:12480): (ubiquitin conjugating enzyme E2 F (putative)) Enables NEDD8 conjugating enzyme activity. Involved in protein neddylation. Predicted to be located in cytosol. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

UBE2F-SCLY (HGNC:48339): (UBE2F-SCLY readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring UBE2F (ubiquitin-conjugating enzyme E2F) and SCLY (selenocysteine lyase) genes on chromosome 2. The read-through transcript is a candidate for non-sense mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38601646).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080678.3. 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
	UBE2F	NM_080678.3	MANE Select	c.73G>T	p.Asp25Tyr	missense	Exon 2 of 10	NP_542409.1	Q969M7-1
	UBE2F	NM_001278305.2		c.73G>T	p.Asp25Tyr	missense	Exon 2 of 10	NP_001265234.1	Q969M7-1
	UBE2F	NM_001278308.2		c.73G>T	p.Asp25Tyr	missense	Exon 2 of 9	NP_001265237.1	Q969M7-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2F	ENST00000272930.9	TSL:1 MANE Select	c.73G>T	p.Asp25Tyr	missense	Exon 2 of 10	ENSP00000272930.4	Q969M7-1
	UBE2F-SCLY	ENST00000449191.1	TSL:3	n.73G>T		non_coding_transcript_exon	Exon 2 of 11	ENSP00000456827.1	H3BSR4
	UBE2F	ENST00000888993.1		c.73G>T	p.Asp25Tyr	missense	Exon 2 of 10	ENSP00000559052.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461746 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.20
Sift	Benign	0.091	T
Sift4G	Uncertain	0.034	D
Polyphen		0.14	B
Vest4		0.76
MutPred		0.32		Gain of catalytic residue at D25 (P = 0.0471)
MVP		0.67
MPC		1.8
ClinPred		0.93	D
GERP RS		5.1
PromoterAI		0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.58
Mutation Taster		=73/27	polymorphism

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: rs968464715; hg19: chr2-238881822;