2-218482092-C-A

Position:

• chr2-218482092-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020935.3(USP37):​c.1813G>T​(p.Gly605Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: USP37 NM_020935.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP37	NM_020935.3	c.1813G>T	p.Gly605Cys	missense_variant	17/26	ENST00000258399.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP37	ENST00000258399.8	c.1813G>T	p.Gly605Cys	missense_variant	17/26	1	NM_020935.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Jan 10, 2023

The c.1813G>T (p.G605C) alteration is located in exon 17 (coding exon 14) of the USP37 gene. This alteration results from a G to T substitution at nucleotide position 1813, causing the glycine (G) at amino acid position 605 to be replaced by a cysteine (C). 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	0.28
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.3	M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.033	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.55
MutPred		0.53		Gain of catalytic residue at G605 (P = 0.0372);Gain of catalytic residue at G605 (P = 0.0372);.;Gain of catalytic residue at G605 (P = 0.0372);
MVP		0.21
MPC		1.0
ClinPred		0.97	D
GERP RS		3.9
Varity_R		0.46
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-219346815;