chr2-218474843-C-T

Variant names:

• chr2-218474843-C-T
• NM_020935.3:c.2086G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020935.3(USP37):​c.2086G>A​(p.Glu696Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: USP37 NM_020935.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

Genes affected

USP37 (HGNC:20063): (ubiquitin specific peptidase 37) Enables cysteine-type endopeptidase activity; protein kinase binding activity; and thiol-dependent deubiquitinase. Involved in G1/S transition of mitotic cell cycle; protein deubiquitination; and regulation of DNA replication. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13599336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020935.3. 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
	USP37	NM_020935.3	MANE Select	c.2086G>A	p.Glu696Lys	missense	Exon 20 of 26	NP_065986.3	Q86T82-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP37	ENST00000258399.8	TSL:1 MANE Select	c.2086G>A	p.Glu696Lys	missense	Exon 20 of 26	ENSP00000258399.3	Q86T82-1
	USP37	ENST00000418019.5	TSL:1	c.2086G>A	p.Glu696Lys	missense	Exon 20 of 26	ENSP00000396585.1	Q86T82-1
	USP37	ENST00000415516.5	TSL:1	c.1804G>A	p.Glu602Lys	missense	Exon 18 of 24	ENSP00000400902.1	Q86T82-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0018	T
Eigen	Benign	0.079
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.4
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.052
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		0.18	B
Vest4		0.16
MutPred		0.35		Gain of ubiquitination at E696 (P = 0.0016)
MVP		0.12
MPC		0.44
ClinPred		0.73	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.17
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

hg19: chr2-219339566;