Variant rs1057744 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002226.5(JAG2):c.1501G>A(p.Glu501Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,560,146 control chromosomes in the GnomAD database, including 212,715 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.58 ( 26926 hom., cov: 34)

Exomes 𝑓: 0.51 ( 185789 hom. )

Consequence

JAG2
NM_002226.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.0454674E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAG2	NM_002226.5 linkuse as main transcript	c.1501G>A	p.Glu501Lys	missense_variant	12/26	ENST00000331782.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAG2	ENST00000331782.8 linkuse as main transcript	c.1501G>A	p.Glu501Lys	missense_variant	12/26	1	NM_002226.5	P1	Q9Y219-1
JAG2	ENST00000347004.2 linkuse as main transcript	c.1387G>A	p.Glu463Lys	missense_variant	11/25	1			Q9Y219-2

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88190

AN:

151978

Hom.:

26892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.764

Gnomad AMI

AF:

0.505

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.588

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.554

GnomAD3 exomes

AF:

0.482

AC:

79977

AN:

165782

Hom.:

20323

AF XY:

0.476

AC XY:

42429

AN XY:

89058

show subpopulations

Gnomad AFR exome

AF:

0.775

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.307

Gnomad SAS exome

AF:

0.384

Gnomad FIN exome

AF:

0.572

Gnomad NFE exome

AF:

0.517

Gnomad OTH exome

AF:

0.512

GnomAD4 exome

AF:

0.509

AC:

716300

AN:

1408050

Hom.:

185789

Cov.:

AF XY:

0.505

AC XY:

351202

AN XY:

695626

show subpopulations

Gnomad4 AFR exome

AF:

0.780

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.522

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.383

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.516

Gnomad4 OTH exome

AF:

0.509

GnomAD4 genome

AF:

0.580

AC:

88262

AN:

152096

Hom.:

26926

Cov.:

AF XY:

0.574

AC XY:

42700

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.764

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.519

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.588

Gnomad4 NFE

AF:

0.531

Gnomad4 OTH

AF:

0.551

Alfa

AF:

0.524

Hom.:

36444

Bravo

AF:

0.580

TwinsUK

AF:

0.518

AC:

1922

ALSPAC

AF:

0.495

AC:

1906

ESP6500AA

AF:

0.763

AC:

3254

ESP6500EA

AF:

0.535

AC:

4465

ExAC

AF:

0.402

AC:

43167

Asia WGS

AF:

0.334

AC:

1163

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.61

D;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0000040

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.17

Sift

Benign

0.24

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0010

B;B

Vest4

0.057

MPC

0.26

ClinPred

0.012

GERP RS

1.4

Varity_R

0.13

gMVP

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over