2-218474843-C-T

Position:

• chr2-218474843-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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]

USP37 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP37	NM_020935.3	c.2086G>A	p.Glu696Lys	missense_variant	20/26	ENST00000258399.8	NP_065986.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP37	ENST00000258399.8	c.2086G>A	p.Glu696Lys	missense_variant	20/26	1	NM_020935.3	ENSP00000258399.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2024

The c.2086G>A (p.E696K) alteration is located in exon 20 (coding exon 17) of the USP37 gene. This alteration results from a G to A substitution at nucleotide position 2086, causing the glutamic acid (E) at amino acid position 696 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.;T
Eigen	Benign	0.079
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	.;.;D;D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.85	N;N;N;N
REVEL	Benign	0.052
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.30	T;T;T;T
Polyphen		0.18	B;B;B;B
Vest4		0.16
MutPred		0.35		Gain of ubiquitination at E696 (P = 0.0016);Gain of ubiquitination at E696 (P = 0.0016);.;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219339566;