rs1057744

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

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

Publications

50 publications found

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:

MIR6765 (HGNC:50030): (microRNA 6765) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6765 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002226.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JAG2	NM_002226.5	MANE Select	c.1501G>A	p.Glu501Lys	missense	Exon 12 of 26	NP_002217.3
JAG2	NM_145159.3		c.1387G>A	p.Glu463Lys	missense	Exon 11 of 25	NP_660142.1	Q9Y219-2
MIR6765	NR_106823.1		n.*73G>A		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JAG2	ENST00000331782.8	TSL:1 MANE Select	c.1501G>A	p.Glu501Lys	missense	Exon 12 of 26	ENSP00000328169.3	Q9Y219-1
JAG2	ENST00000347004.2	TSL:1	c.1387G>A	p.Glu463Lys	missense	Exon 11 of 25	ENSP00000328566.2	Q9Y219-2
JAG2	ENST00000938643.1		c.1504G>A	p.Glu502Lys	missense	Exon 12 of 26	ENSP00000608702.1

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

GnomAD2 exomes

AF:

0.482

AC:

79977

AN:

165782

AF XY:

0.476

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 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

African (AFR)

AF:

0.780

AC:

24989

AN:

32044

American (AMR)

AF:

0.398

AC:

14688

AN:

36928

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

13173

AN:

25252

East Asian (EAS)

AF:

0.330

AC:

12102

AN:

36622

South Asian (SAS)

AF:

0.383

AC:

30722

AN:

80290

European-Finnish (FIN)

AF:

0.578

AC:

27924

AN:

48294

Middle Eastern (MID)

AF:

0.557

AC:

3180

AN:

5710

European-Non Finnish (NFE)

AF:

0.516

AC:

559844

AN:

1084556

Other (OTH)

AF:

0.509

AC:

29678

AN:

58354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

22819

45638

68457

91276

114095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16180

32360

48540

64720

80900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.580

AC:

88262

AN:

152096

Hom.:

26926

Cov.:

AF XY:

0.574

AC XY:

42700

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.764

AC:

31718

AN:

41492

American (AMR)

AF:

0.472

AC:

7217

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1801

AN:

3472

East Asian (EAS)

AF:

0.326

AC:

1686

AN:

5168

South Asian (SAS)

AF:

0.364

AC:

1755

AN:

4826

European-Finnish (FIN)

AF:

0.588

AC:

6234

AN:

10606

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.531

AC:

36050

AN:

67926

Other (OTH)

AF:

0.551

AC:

1162

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1856

3712

5568

7424

9280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.529

Hom.:

77427

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0000041

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

PhyloP100

0.074

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

REVEL

Benign

0.17

Sift

Benign

0.24

Sift4G

Benign

0.16

Polyphen

0.0010

Vest4

0.057

MPC

0.26

ClinPred

0.012

GERP RS

1.4

Varity_R

0.13

gMVP

0.78

Mutation Taster

=93/7

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over