5-134578574-A-G

Position:

• chr5-134578574-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001388185.1(JADE2):​c.1762A>G​(p.Asn588Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: JADE2 NM_001388185.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.91

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053218007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JADE2	NM_001388185.1	c.1762A>G	p.Asn588Asp	missense_variant	12/12	ENST00000681547.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JADE2	ENST00000681547.2	c.1762A>G	p.Asn588Asp	missense_variant	12/12		NM_001388185.1	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.1630A>G (p.N544D) alteration is located in exon 11 (coding exon 10) of the JADE2 gene. This alteration results from a A to G substitution at nucleotide position 1630, causing the asparagine (N) at amino acid position 544 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.0072	T;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.053	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	.;.;N
MutationTaster	Benign	1.0	D;N;N;N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.14	N;N;N
REVEL	Benign	0.072
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.21
MutPred		0.23		.;.;Gain of phosphorylation at T541 (P = 0.1088);
MVP		0.27
MPC		0.86
ClinPred		0.16	T
GERP RS		4.2
Varity_R		0.076
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-133914264;