2-61188176-G-A

Variant names:

• chr2-61188176-G-A
• rs184080617
• NM_014709.4:c.10567C>T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014709.4(USP34):​c.10567C>T​(p.Leu3523Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000914 in 1,614,118 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (4 hom.)
• Consequence: USP34 NM_014709.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.18

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]

AHSA2P (HGNC:20437): (activator of HSP90 ATPase homolog 2, pseudogene) Predicted to enable ATPase activator activity. Predicted to be involved in positive regulation of ATPase activity and protein folding. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-61188176-G-A is Benign according to our data. Variant chr2-61188176-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 723882.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP34	NM_014709.4	c.10567C>T	p.Leu3523Leu	synonymous_variant	Exon 80 of 80	ENST00000398571.7	NP_055524.3
AHSA2P	NR_152210.1	n.2366G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP34	ENST00000398571.7	c.10567C>T	p.Leu3523Leu	synonymous_variant	Exon 80 of 80	5	NM_014709.4	ENSP00000381577.2
AHSA2P	ENST00000394457.7	n.3547G>A		non_coding_transcript_exon_variant	Exon 6 of 6	1
USP34	ENST00000411912.5	c.3595C>T	p.Leu1199Leu	synonymous_variant	Exon 26 of 26	5		ENSP00000398960.1
USP34	ENST00000436269.1	c.1201C>T	p.Leu401Leu	synonymous_variant	Exon 7 of 7	5		ENSP00000398489.1

Frequencies

GnomAD3 genomes AF: 0.000565 AC: 86 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000663 AC: 165 AN: 249054 Hom.: 0 AF XY: 0.000725 AC XY: 98 AN XY: 135128

Gnomad AFR exome AF: 0.000259

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00108

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000930

Gnomad OTH exome AF: 0.000496

GnomAD4 exome AF: 0.000951 AC: 1390 AN: 1461870 Hom.: 4 Cov.: 30 AF XY: 0.000963 AC XY: 700 AN XY: 727236

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00105

Gnomad4 OTH exome AF: 0.000993

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33 AN XY: 74448

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000747 Hom.: 0

Bravo AF: 0.000540

EpiCase AF: 0.00142

EpiControl AF: 0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.7
DANN	Benign	0.89

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: rs184080617; hg19: chr2-61415311;