rs2593633

Variant names:

• chr2-61344378-T-C
• rs2593633
• NM_014709.4:c.2286-349A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014709.4(USP34):​c.2286-349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,050 control chromosomes in the GnomAD database, including 10,299 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 0.37 (10299 hom., cov: 32)
• Consequence: USP34 NM_014709.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 9 publications found

Genes affected

USP34 (HGNC:20066): (ubiquitin specific peptidase 34) Enables cysteine-type endopeptidase activity and thiol-dependent deubiquitinase. Involved in positive regulation of canonical Wnt signaling pathway and protein K48-linked deubiquitination. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

USP34 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014709.4. 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
	USP34	NM_014709.4	MANE Select	c.2286-349A>G		intron	N/A	NP_055524.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP34	ENST00000398571.7	TSL:5 MANE Select	c.2286-349A>G		intron	N/A	ENSP00000381577.2	Q70CQ2-1
	USP34	ENST00000460004.1	TSL:4	n.251-349A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55941 AN: 151930 Hom.: 10296 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.368 AC: 55969 AN: 152050 Hom.: 10299 Cov.: 32 AF XY: 0.363 AC XY: 26966 AN XY: 74342

African (AFR) AF: 0.391 AC: 16209 AN: 41452

American (AMR) AF: 0.336 AC: 5137 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1657 AN: 5170

South Asian (SAS) AF: 0.374 AC: 1807 AN: 4826

European-Finnish (FIN) AF: 0.323 AC: 3415 AN: 10570

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25576 AN: 67974

Other (OTH) AF: 0.336 AC: 709 AN: 2112

Alfa AF: 0.378 Hom.: 2666

Bravo AF: 0.368

Asia WGS AF: 0.357 AC: 1238 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs2593633; hg19: chr2-61571513;