chr2-218510941-G-A

Position:

• chr2-218510941-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020935.3(USP37):​c.864-801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 152,116 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.040 (158 hom., cov: 32)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP37	NM_020935.3	c.864-801C>T		intron_variant		ENST00000258399.8	NP_065986.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP37	ENST00000258399.8	c.864-801C>T		intron_variant		1	NM_020935.3	ENSP00000258399	P1

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6082 AN: 152000 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.0378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0400 AC: 6085 AN: 152116 Hom.: 158 Cov.: 32 AF XY: 0.0393 AC XY: 2922 AN XY: 74386

Gnomad4 AFR AF: 0.0519

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0432

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0366 Hom.: 8

Bravo AF: 0.0409

Asia WGS AF: 0.0680 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.25

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

LitVar

Other links and lift over

dbSNP: rs7565544; hg19: chr2-219375664;