Variant 14-105142691-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002226.5(JAG2):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,590,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

JAG2
NM_002226.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.74

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 14-105142691-G-A is Benign according to our data. Variant chr14-105142691-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3033613.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
JAG2	NM_002226.5 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	26/26	ENST00000331782.8
JAG2	NM_145159.3 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	25/25
JAG2	XM_047431352.1 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	25/25
JAG2	XM_047431353.1 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	24/24

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAG2	ENST00000331782.8 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	26/26	1	NM_002226.5	P1	Q9Y219-1
JAG2	ENST00000347004.2 linkuse as main transcript	c.*4C>T	3_prime_UTR_variant	25/25	1			Q9Y219-2
JAG2	ENST00000546616.1 linkuse as main transcript	n.1339C>T	non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00406

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000501

AC:

104

AN:

207672

Hom.:

AF XY:

0.000533

AC XY:

AN XY:

114400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00515

Gnomad SAS exome

AF:

0.000337

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.000383

GnomAD4 exome

AF:

0.000196

AC:

282

AN:

1438526

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

165

AN XY:

713744

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00419

Gnomad4 SAS exome

AF:

0.000591

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000345

Gnomad4 OTH exome

AF:

0.000539

GnomAD4 genome

AF:

0.000282

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00407

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.000230

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

JAG2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 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

-0.94

CADD

Benign

5.8

DANN

Benign

0.73

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