Variant chr14-105168369-C-CCAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PM4_SupportingBP6_ModerateBS1BS2

The NM_002226.5(JAG2):c.49_51dupCTG(p.Leu17dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 1,011,200 control chromosomes in the GnomAD database, including 456 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 67 hom., cov: 30)

Exomes 𝑓: 0.035 ( 389 hom. )

Consequence

JAG2
NM_002226.5 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.245

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:

ENSG00000257622 (HGNC:):

ENSG00000257622 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_002226.5. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 14-105168369-C-CCAG is Benign according to our data. Variant chr14-105168369-C-CCAG is described in ClinVar as [Benign]. Clinvar id is 402990.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.024 (3504/145738) while in subpopulation NFE AF= 0.0394 (2581/65506). AF 95% confidence interval is 0.0381. There are 67 homozygotes in gnomad4. There are 1570 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAG2	NM_002226.5 linkuse as main transcript	c.49_51dupCTG	p.Leu17dup	conservative_inframe_insertion	1/26	ENST00000331782.8	NP_002217.3	Q9Y219-1
JAG2	NM_145159.3 linkuse as main transcript	c.49_51dupCTG	p.Leu17dup	conservative_inframe_insertion	1/25		NP_660142.1	Q9Y219-2
JAG2	XM_047431354.1 linkuse as main transcript	c.49_51dupCTG	p.Leu17dup	conservative_inframe_insertion	1/18		XP_047287310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
JAG2	ENST00000331782.8 linkuse as main transcript	c.49_51dupCTG	p.Leu17dup	conservative_inframe_insertion	1/26	1	NM_002226.5	ENSP00000328169.3	Q9Y219-1
JAG2	ENST00000347004.2 linkuse as main transcript	c.49_51dupCTG	p.Leu17dup	conservative_inframe_insertion	1/25	1		ENSP00000328566.2	Q9Y219-2
ENSG00000257622	ENST00000548203.1 linkuse as main transcript	n.67-10609_67-10607dupCTG		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3503

AN:

145650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00773

Gnomad AMI

AF:

0.0246

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.0234

Gnomad EAS

AF:

0.000983

Gnomad SAS

AF:

0.0260

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.0226

Gnomad NFE

AF:

0.0394

Gnomad OTH

AF:

0.0204

GnomAD3 exomes

AF:

0.0198

AC:

815

AN:

41072

Hom.:

AF XY:

0.0231

AC XY:

561

AN XY:

24318

show subpopulations

Gnomad AFR exome

AF:

0.00820

Gnomad AMR exome

AF:

0.00664

Gnomad ASJ exome

AF:

0.0160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0241

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0165

GnomAD4 exome

AF:

0.0351

AC:

30373

AN:

865462

Hom.:

389

Cov.:

AF XY:

0.0351

AC XY:

14673

AN XY:

417802

show subpopulations

Gnomad4 AFR exome

AF:

0.00429

Gnomad4 AMR exome

AF:

0.00847

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.000457

Gnomad4 SAS exome

AF:

0.0265

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0372

Gnomad4 OTH exome

AF:

0.0314

GnomAD4 genome

AF:

0.0240

AC:

3504

AN:

145738

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1570

AN XY:

70932

show subpopulations

Gnomad4 AFR

AF:

0.00771

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.0234

Gnomad4 EAS

AF:

0.000986

Gnomad4 SAS

AF:

0.0256

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.0394

Gnomad4 OTH

AF:

0.0202

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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