NM_016076.5:c.167C>G

Variant names:

• chr1-244689300-C-G
• rs759987328
• NM_016076.5:c.167C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_016076.5(DESI2):​c.167C>G​(p.Ser56Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,590,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: DESI2 NM_016076.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3277368).
• BS2: High AC in GnomAdExome4 at 18 AD gene.

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.167C>G	p.Ser56Cys	missense	Exon 3 of 5	NP_057160.2
	DESI2	NM_001297746.2		c.116-2584C>G		intron	N/A	NP_001284675.1	Q9BSY9-2
	DESI2	NR_123735.2		n.355C>G		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DESI2	ENST00000302550.16	TSL:1 MANE Select	c.167C>G	p.Ser56Cys	missense	Exon 3 of 5	ENSP00000306528.11	Q9BSY9-1
	DESI2	ENST00000263831.11	TSL:1	c.116-2584C>G		intron	N/A	ENSP00000263831.7	Q9BSY9-2
	DESI2	ENST00000859654.1		c.227C>G	p.Ser76Cys	missense	Exon 4 of 6	ENSP00000529713.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152042 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

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: 0.0000319 AC: 8 AN: 250484 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000125 AC: 18 AN: 1438498 Hom.: 0 Cov.: 26 AF XY: 0.0000139 AC XY: 10 AN XY: 717106

African (AFR) AF: 0.00 AC: 0 AN: 33000

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 15 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.00 AC: 0 AN: 85506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1091078

Other (OTH) AF: 0.0000335 AC: 2 AN: 59646

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152042 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74278

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000130 Hom.: 0

ExAC AF: 0.0000330 AC: 4

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	0.096
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.41
Sift	Benign	0.041	D
Sift4G	Uncertain	0.040	D
Polyphen		0.95	P
Vest4		0.47
MutPred		0.36		Loss of disorder (P = 0.0018)
MVP		0.14
MPC		2.1
ClinPred		0.39	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.37
gMVP		0.78
Mutation Taster		=37/63	disease causing

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: rs759987328; hg19: chr1-244852602;