13-99220179-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144072.2(UBAC2):c.32-18248G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,006 control chromosomes in the GnomAD database, including 22,947 homozygotes. 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: 𝑓 0.53 (22947 hom., cov: 32)
• Consequence: UBAC2 NM_001144072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

Genes affected

UBAC2 (HGNC:20486): (UBA domain containing 2) Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of retrograde protein transport, ER to cytosol. Acts upstream of or within protein localization to endoplasmic reticulum. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBAC2	NM_001144072.2	c.32-18248G>C		intron_variant		ENST00000403766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBAC2	ENST00000403766.8	c.32-18248G>C		intron_variant		2	NM_001144072.2	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81006 AN: 151888 Hom.: 22935 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.542

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.533 AC: 81052 AN: 152006 Hom.: 22947 Cov.: 32 AF XY: 0.526 AC XY: 39084 AN XY: 74298

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.540

Alfa AF: 0.578 Hom.: 3154

Bravo AF: 0.528

Asia WGS AF: 0.415 AC: 1438 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.72
Dann	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs984477; hg19: chr13-99872433;