2-23971397-G-T

Variant names:

• chr2-23971397-G-T
• rs772925376
• NM_181713.4:c.163G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181713.4(UBXN2A):​c.163G>T​(p.Ala55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict 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. A55T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: UBXN2A NM_181713.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 0 publications found

Genes affected

UBXN2A (HGNC:27265): (UBX domain protein 2A) Predicted to enable ubiquitin binding activity. Predicted to be involved in several processes, including autophagosome assembly; nuclear membrane reassembly; and proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to act upstream of or within cellular response to leukemia inhibitory factor; regulation of gene expression; and regulation of protein metabolic process. Predicted to be located in cis-Golgi network and endoplasmic reticulum. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181713.4. 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
	UBXN2A	NM_181713.4	MANE Select	c.163G>T	p.Ala55Ser	missense	Exon 3 of 7	NP_859064.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN2A	ENST00000309033.5	TSL:1 MANE Select	c.163G>T	p.Ala55Ser	missense	Exon 3 of 7	ENSP00000312107.4	P68543-1
	UBXN2A	ENST00000446425.2	TSL:1	n.625G>T		non_coding_transcript_exon	Exon 4 of 8
	UBXN2A	ENST00000404924.5	TSL:2	c.163G>T	p.Ala55Ser	missense	Exon 4 of 8	ENSP00000385525.1	P68543-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000823 AC: 2 AN: 243124 AF XY: 0.00000762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1395242 Hom.: 0 Cov.: 29 AF XY: 0.00000146 AC XY: 1 AN XY: 685464

African (AFR) AF: 0.00 AC: 0 AN: 32494

American (AMR) AF: 0.00 AC: 0 AN: 42114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24800

East Asian (EAS) AF: 0.00 AC: 0 AN: 38504

South Asian (SAS) AF: 0.00 AC: 0 AN: 74818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5460

European-Non Finnish (NFE) AF: 0.00000281 AC: 3 AN: 1068118

Other (OTH) AF: 0.00 AC: 0 AN: 57180

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000165 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.3
DANN	Benign	0.60
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.14
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.014
Sift	Benign	0.49	T
Sift4G	Benign	0.58	T
Polyphen		0.0030	B
Vest4		0.083
MutPred		0.25		Gain of disorder (P = 0.033)
MVP		0.25
MPC		0.11
ClinPred		0.027	T
GERP RS		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.13
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: -25

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs772925376; hg19: chr2-24194267;