rs374254320

Variant names:

• chr19-50510383-C-A
• rs374254320
• NM_001270639.2:c.49G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-50510383-C-A
• chr19-50510383-C-G
• chr19-50510383-C-T

Variant summary

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

The NM_001270639.2(JOSD2):​c.49G>T​(p.Glu17*) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000219 in 1,461,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: JOSD2 NM_001270639.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• Publications: 1 publications found

Genes affected

JOSD2 (HGNC:28853): (Josephin domain containing 2) This gene encodes a protein containing a Josephin domain. Josephin domain-containing proteins are deubiquitinating enzymes which catalyze the hydrolysis of the bond between the C-terminal glycine of the ubiquitin peptide and protein substrates. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270639.2. 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
	JOSD2	NM_001270639.2	MANE Select	c.49G>T	p.Glu17*	stop_gained	Exon 2 of 5	NP_001257568.1	Q8TAC2-1
	JOSD2	NM_001270640.2		c.49G>T	p.Glu17*	stop_gained	Exon 2 of 5	NP_001257569.1	Q8TAC2-1
	JOSD2	NM_001270686.2		c.49G>T	p.Glu17*	stop_gained	Exon 2 of 5	NP_001257615.1	Q8TAC2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JOSD2	ENST00000598418.6	TSL:1 MANE Select	c.49G>T	p.Glu17*	stop_gained	Exon 2 of 5	ENSP00000468956.2	Q8TAC2-1
	JOSD2	ENST00000601423.5	TSL:1	c.49G>T	p.Glu17*	stop_gained	Exon 2 of 5	ENSP00000472116.1	Q8TAC2-1
	JOSD2	ENST00000884030.1		c.49G>T	p.Glu17*	stop_gained	Exon 2 of 5	ENSP00000554089.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248686 AF XY: 0.00000742

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: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461074 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 726832

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52812

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5756

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111876

Other (OTH) AF: 0.0000166 AC: 1 AN: 60376

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	0.79
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.90	D
PhyloP100		4.4
Vest4		0.26
GERP RS		2.1
Mutation Taster		=11/189	disease causing (fs/PTC)

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: rs374254320; hg19: chr19-51013640;