13-99381398-A-G

Variant summary

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

The NM_001144072.2(UBAC2):c.928-3830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,256 control chromosomes in the GnomAD database, including 49,057 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 0.80 (49057 hom., cov: 33)
• Consequence: UBAC2 NM_001144072.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBAC2	NM_001144072.2	c.928-3830A>G		intron_variant		ENST00000403766.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBAC2	ENST00000403766.8	c.928-3830A>G		intron_variant		2	NM_001144072.2	P1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121345 AN: 152138 Hom.: 49042 Cov.: 33

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.797 AC: 121402 AN: 152256 Hom.: 49057 Cov.: 33 AF XY: 0.796 AC XY: 59291 AN XY: 74456

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.765

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.805

Alfa AF: 0.823 Hom.: 10111

Bravo AF: 0.785

Asia WGS AF: 0.684 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.092
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs912129; hg19: chr13-100033652; COSMIC: COSV63117953; COSMIC: COSV63117953;