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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN2B	NM_001077619.2	c.84+134G>T		intron_variant	Intron 1 of 7	ENST00000399598.7	NP_001071087.1
UBXN2B	NM_001363181.1	c.84+134G>T		intron_variant	Intron 1 of 6		NP_001350110.1
UBXN2B	NM_001330535.2	c.84+134G>T		intron_variant	Intron 1 of 5		NP_001317464.1
UBXN2B	NR_156456.1	n.109+134G>T		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN2B	ENST00000399598.7	c.84+134G>T		intron_variant	Intron 1 of 7	1	NM_001077619.2	ENSP00000382507.2
UBXN2B	ENST00000520732.5	n.84+134G>T		intron_variant	Intron 1 of 5	3		ENSP00000427759.1
UBXN2B	ENST00000522978.1	n.111+134G>T		intron_variant	Intron 1 of 6	3
UBXN2B	ENST00000523409.5	n.84+134G>T		intron_variant	Intron 1 of 8	5		ENSP00000428314.1

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 v4.3

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;