rs866322508

Variant names:

• chr2-218476866-C-G
• NM_020935.3:c.2017G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-218476866-C-G
• chr2-218476866-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.2017G>C​(p.Glu673Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,562 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: USP37 NM_020935.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.88

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24177444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP37	NM_020935.3	c.2017G>C	p.Glu673Gln	missense_variant	Exon 19 of 26	ENST00000258399.8	NP_065986.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP37	ENST00000258399.8	c.2017G>C	p.Glu673Gln	missense_variant	Exon 19 of 26	1	NM_020935.3	ENSP00000258399.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450562 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 721620

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: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0052	T;T;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L;L;.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.051	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.90	P;P;P;P
Vest4		0.25
MutPred		0.32		Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;Loss of helix (P = 0.079);
MVP		0.36
MPC		0.34
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.32

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: chr2-219341589;