Variant chr14-105142941-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002226.5(JAG2):c.3471G>A(p.Pro1157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,608,884 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0029 ( 6 hom. )

Consequence

JAG2
NM_002226.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.920

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-105142941-C-T is Benign according to our data. Variant chr14-105142941-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2644900.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.92 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
JAG2	NM_002226.5 linkuse as main transcript	c.3471G>A	p.Pro1157=	synonymous_variant	26/26	ENST00000331782.8	NP_002217.3
JAG2	NM_145159.3 linkuse as main transcript	c.3357G>A	p.Pro1119=	synonymous_variant	25/25		NP_660142.1
JAG2	XM_047431352.1 linkuse as main transcript	c.3129G>A	p.Pro1043=	synonymous_variant	25/25		XP_047287308.1
JAG2	XM_047431353.1 linkuse as main transcript	c.3015G>A	p.Pro1005=	synonymous_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.3471G>A	p.Pro1157=	synonymous_variant	26/26	1	NM_002226.5	ENSP00000328169	P1	Q9Y219-1
JAG2	ENST00000347004.2 linkuse as main transcript	c.3357G>A	p.Pro1119=	synonymous_variant	25/25	1		ENSP00000328566		Q9Y219-2
JAG2	ENST00000546616.1 linkuse as main transcript	n.1089G>A		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

284

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00188

AC:

438

AN:

233172

Hom.:

AF XY:

0.00173

AC XY:

223

AN XY:

128846

show subpopulations

Gnomad AFR exome

AF:

0.000722

Gnomad AMR exome

AF:

0.000707

Gnomad ASJ exome

AF:

0.00273

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00172

Gnomad NFE exome

AF:

0.00325

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00287

AC:

4187

AN:

1456586

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

2039

AN XY:

724282

show subpopulations

Gnomad4 AFR exome

AF:

0.000450

Gnomad4 AMR exome

AF:

0.000629

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.0000758

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00253

Gnomad4 NFE exome

AF:

0.00345

Gnomad4 OTH exome

AF:

0.00208

GnomAD4 genome

AF:

0.00186

AC:

284

AN:

152298

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00260

Hom.:

Bravo

AF:

0.00187

EpiCase

AF:

0.00202

EpiControl

AF:

0.00267

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

JAG2: BP4, BP7 -

JAG2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.24

DANN

Benign

0.57

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over