5-134576856-G-GA

Position:

• chr5-134576856-G-GA

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001388185.1(JADE2):​c.1644dup​(p.Val549SerfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: JADE2 NM_001388185.1 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.68

Genes affected

JADE2 (HGNC:22984): (jade family PHD finger 2) Predicted to enable ubiquitin protein ligase activity. Involved in histone acetylation. Located in nucleoplasm. Part of histone acetyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.345 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JADE2	NM_001388185.1	c.1644dup	p.Val549SerfsTer6	frameshift_variant	11/12	ENST00000681547.2	NP_001375114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JADE2	ENST00000681547.2	c.1644dup	p.Val549SerfsTer6	frameshift_variant	11/12		NM_001388185.1	ENSP00000505514	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

JADE2-associated Neurodevelopmental Disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

New York Genome Center

Aug 06, 2021

The de novo c.1644dup (p.Val549SerfsTer6) variant identified in the JADE2 gene is the duplication of a single nucleotide, resulting in a frameshift at amino acid 549/835 (exon 11/12). This variant is absent from gnomAD(v3.1.1) suggesting it is not a common benign variant in the populations represented in that database. It is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The de novo c.1644dup (p.Val549SerfsTer6) variant identified in the JADE2 gene is reported as a Variant of Uncertain Significance in a Gene of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-133912546;