chr2-218518968-A-C

Variant names:

• chr2-218518968-A-C
• rs13014473
• NM_020935.3:c.864-8828T>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.864-8828T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 152,260 control chromosomes in the GnomAD database, including 359 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 (359 hom., cov: 32)
• Consequence: USP37 NM_020935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020935.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP37	NM_020935.3	MANE Select	c.864-8828T>G		intron	N/A	NP_065986.3	Q86T82-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP37	ENST00000258399.8	TSL:1 MANE Select	c.864-8828T>G		intron	N/A	ENSP00000258399.3	Q86T82-1
	USP37	ENST00000418019.5	TSL:1	c.864-8828T>G		intron	N/A	ENSP00000396585.1	Q86T82-1
	USP37	ENST00000415516.5	TSL:1	c.648-8828T>G		intron	N/A	ENSP00000400902.1	Q86T82-2

Frequencies

GnomAD3 genomes AF: 0.0566 AC: 8612 AN: 152142 Hom.: 358 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: 0.116

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0567 AC: 8626 AN: 152260 Hom.: 359 Cov.: 32 AF XY: 0.0553 AC XY: 4114 AN XY: 74448

African (AFR) AF: 0.110 AC: 4571 AN: 41528

American (AMR) AF: 0.0278 AC: 426 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3468

East Asian (EAS) AF: 0.117 AC: 605 AN: 5180

South Asian (SAS) AF: 0.0442 AC: 213 AN: 4822

European-Finnish (FIN) AF: 0.0272 AC: 289 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0335 AC: 2280 AN: 68024

Other (OTH) AF: 0.0468 AC: 99 AN: 2116

Alfa AF: 0.0426 Hom.: 420

Bravo AF: 0.0599

Asia WGS AF: 0.0720 AC: 251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-0.94
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: rs13014473; hg19: chr2-219383691;