Variant chr14-105142851-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002226.5(JAG2):c.3561G>C(p.Glu1187Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,568 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

JAG2
NM_002226.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.285

Variant links:

Genes affected

JAG2 (HGNC:6189): (jagged canonical Notch ligand 2) The Notch signaling pathway is an intercellular signaling mechanism that is essential for proper embryonic development. Members of the Notch gene family encode transmembrane receptors that are critical for various cell fate decisions. The protein encoded by this gene is one of several ligands that activate Notch and related receptors. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

JAG2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.078009725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
JAG2	NM_002226.5 linkuse as main transcript	c.3561G>C	p.Glu1187Asp	missense_variant	26/26	ENST00000331782.8	NP_002217.3
JAG2	NM_145159.3 linkuse as main transcript	c.3447G>C	p.Glu1149Asp	missense_variant	25/25		NP_660142.1
JAG2	XM_047431352.1 linkuse as main transcript	c.3219G>C	p.Glu1073Asp	missense_variant	25/25		XP_047287308.1
JAG2	XM_047431353.1 linkuse as main transcript	c.3105G>C	p.Glu1035Asp	missense_variant	24/24		XP_047287309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAG2	ENST00000331782.8 linkuse as main transcript	c.3561G>C	p.Glu1187Asp	missense_variant	26/26	1	NM_002226.5	ENSP00000328169	P1	Q9Y219-1
JAG2	ENST00000347004.2 linkuse as main transcript	c.3447G>C	p.Glu1149Asp	missense_variant	25/25	1		ENSP00000328566		Q9Y219-2
JAG2	ENST00000546616.1 linkuse as main transcript	n.1179G>C		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724254

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.3561G>C (p.E1187D) alteration is located in exon 26 (coding exon 26) of the JAG2 gene. This alteration results from a G to C substitution at nucleotide position 3561, causing the glutamic acid (E) at amino acid position 1187 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

0.089

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.38

T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.61

T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.19

Sift

Benign

0.40

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.0030

B;B

Vest4

0.062

MutPred

0.054

Loss of helix (P = 0.3949);.;

MVP

0.47

MPC

0.21

ClinPred

0.035

GERP RS

2.5

Varity_R

0.032

gMVP

0.021

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over