2-218461578-T-C

Variant names:

• chr2-218461578-T-C
• rs13006838
• NM_020935.3:c.2528-1673A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020935.3(USP37):​c.2528-1673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 152,032 control chromosomes in the GnomAD database, including 361 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 0.057 (361 hom., cov: 32)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USP37	NM_020935.3	c.2528-1673A>G		intron_variant	Intron 22 of 25	ENST00000258399.8	NP_065986.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP37	ENST00000258399.8	c.2528-1673A>G		intron_variant	Intron 22 of 25	1	NM_020935.3	ENSP00000258399.3
USP37	ENST00000418019.5	c.2528-1673A>G		intron_variant	Intron 22 of 25	1		ENSP00000396585.1
USP37	ENST00000415516.5	c.2246-1673A>G		intron_variant	Intron 20 of 23	1		ENSP00000400902.1
USP37	ENST00000454775.5	c.2528-1673A>G		intron_variant	Intron 22 of 25	2		ENSP00000393662.1

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8622 AN: 151914 Hom.: 360 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0568 AC: 8636 AN: 152032 Hom.: 361 Cov.: 32 AF XY: 0.0554 AC XY: 4120 AN XY: 74302

African (AFR) AF: 0.110 AC: 4575 AN: 41452

American (AMR) AF: 0.0279 AC: 426 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3472

East Asian (EAS) AF: 0.117 AC: 606 AN: 5170

South Asian (SAS) AF: 0.0446 AC: 215 AN: 4818

European-Finnish (FIN) AF: 0.0271 AC: 286 AN: 10538

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0336 AC: 2286 AN: 67988

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0404 Hom.: 80

Bravo AF: 0.0600

Asia WGS AF: 0.0720 AC: 251 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	4.2
DANN	Benign	0.82
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13006838; hg19: chr2-219326301;