rs1292697705

Variant names:

• chr1-244691910-C-G
• rs1292697705
• NM_016076.5:c.241C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016076.5(DESI2):​c.241C>G​(p.Leu81Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000125 in 1,595,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DESI2 NM_016076.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20
• Publications: 0 publications found

Genes affected

DESI2 (HGNC:24264): (desumoylating isopeptidase 2) Enables Lys48-specific deubiquitinase activity; Lys63-specific deubiquitinase activity; and thiol-dependent deubiquitinase. Predicted to be involved in protein deubiquitination. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19672245).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016076.5. 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
	DESI2	NM_016076.5	MANE Select	c.241C>G	p.Leu81Val	missense	Exon 4 of 5	NP_057160.2
	DESI2	NM_001297746.2		c.142C>G	p.Leu48Val	missense	Exon 3 of 4	NP_001284675.1	Q9BSY9-2
	DESI2	NR_123735.2		n.424C>G		non_coding_transcript_exon	Exon 4 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DESI2	ENST00000302550.16	TSL:1 MANE Select	c.241C>G	p.Leu81Val	missense	Exon 4 of 5	ENSP00000306528.11	Q9BSY9-1
	DESI2	ENST00000263831.11	TSL:1	c.142C>G	p.Leu48Val	missense	Exon 3 of 4	ENSP00000263831.7	Q9BSY9-2
	DESI2	ENST00000859654.1		c.301C>G	p.Leu101Val	missense	Exon 5 of 6	ENSP00000529713.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151866 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000427 AC: 1 AN: 234384 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000912

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443414 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 718094

African (AFR) AF: 0.00 AC: 0 AN: 32422

American (AMR) AF: 0.00 AC: 0 AN: 39190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25816

East Asian (EAS) AF: 0.00 AC: 0 AN: 38794

South Asian (SAS) AF: 0.00 AC: 0 AN: 81788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5034

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107542

Other (OTH) AF: 0.00 AC: 0 AN: 59554

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151866 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74152

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41336

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67936

Other (OTH) AF: 0.00 AC: 0 AN: 2084

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000508 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	0.013
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.60	N
PhyloP100		5.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.064
Sift	Benign	0.35	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.36		Loss of stability (P = 0.1454)
MVP		0.14
MPC		1.1
ClinPred		0.42	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.72
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1292697705; hg19: chr1-244855212;