8-58411603-G-T

Variant names:

• chr8-58411603-G-T
• rs2859998
• NM_001077619.2:c.84+134G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077619.2(UBXN2B):​c.84+134G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000565 in 530,572 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: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: UBXN2B NM_001077619.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 17 publications found

Genes affected

UBXN2B (HGNC:27035): (UBX domain protein 2B) Predicted to enable ubiquitin binding activity. Involved in establishment of mitotic spindle orientation; negative regulation of protein localization to centrosome; and positive regulation of mitotic centrosome separation. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and spindle pole centrosome. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077619.2. 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
	UBXN2B	NM_001077619.2	MANE Select	c.84+134G>T		intron	N/A	NP_001071087.1	Q14CS0
	UBXN2B	NM_001363181.1		c.84+134G>T		intron	N/A	NP_001350110.1
	UBXN2B	NM_001330535.2		c.84+134G>T		intron	N/A	NP_001317464.1	E5RJ36

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN2B	ENST00000399598.7	TSL:1 MANE Select	c.84+134G>T		intron	N/A	ENSP00000382507.2	Q14CS0
	UBXN2B	ENST00000970427.1		c.84+134G>T		intron	N/A	ENSP00000640486.1
	UBXN2B	ENST00000879981.1		c.84+134G>T		intron	N/A	ENSP00000550040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000565 AC: 3 AN: 530572 Hom.: 0 AF XY: 0.00000770 AC XY: 2 AN XY: 259594

African (AFR) AF: 0.00 AC: 0 AN: 12496

American (AMR) AF: 0.00 AC: 0 AN: 7660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10906

East Asian (EAS) AF: 0.00 AC: 0 AN: 23910

South Asian (SAS) AF: 0.00 AC: 0 AN: 8496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1876

European-Non Finnish (NFE) AF: 0.00000716 AC: 3 AN: 418772

Other (OTH) AF: 0.00 AC: 0 AN: 25466

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 23434

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		-0.31
PromoterAI		0.043	Neutral

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: rs2859998; hg19: chr8-59324162;