chr2-218495852-T-G

Position:

• chr2-218495852-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020935.3(USP37):​c.1380A>C​(p.Glu460Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: USP37 NM_020935.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036536276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP37	NM_020935.3	c.1380A>C	p.Glu460Asp	missense_variant	14/26	ENST00000258399.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP37	ENST00000258399.8	c.1380A>C	p.Glu460Asp	missense_variant	14/26	1	NM_020935.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0025	T;T;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.037	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.21	N;N;.;N
MutationTaster	Benign	0.58	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.40	T;T;T;T
Sift4G	Benign	0.60	T;T;T;T
Polyphen		0.0020	B;B;B;B
Vest4		0.10
MutPred		0.34		Loss of glycosylation at S462 (P = 0.1047);Loss of glycosylation at S462 (P = 0.1047);.;Loss of glycosylation at S462 (P = 0.1047);
MVP		0.043
MPC		0.28
ClinPred		0.21	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219360575;