14-105142821-G-A

Position:

• chr14-105142821-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_002226.5(JAG2):​c.3591C>T​(p.Leu1197=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: JAG2 NM_002226.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.670

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-105142821-G-A is Benign according to our data. Variant chr14-105142821-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.67 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAG2	NM_002226.5	c.3591C>T	p.Leu1197=	synonymous_variant	26/26	ENST00000331782.8	NP_002217.3
JAG2	NM_145159.3	c.3477C>T	p.Leu1159=	synonymous_variant	25/25		NP_660142.1
JAG2	XM_047431352.1	c.3249C>T	p.Leu1083=	synonymous_variant	25/25		XP_047287308.1
JAG2	XM_047431353.1	c.3135C>T	p.Leu1045=	synonymous_variant	24/24		XP_047287309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAG2	ENST00000331782.8	c.3591C>T	p.Leu1197=	synonymous_variant	26/26	1	NM_002226.5	ENSP00000328169	P1
JAG2	ENST00000347004.2	c.3477C>T	p.Leu1159=	synonymous_variant	25/25	1		ENSP00000328566
JAG2	ENST00000546616.1	n.1209C>T		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

JAG2: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.61

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

Other links and lift over

dbSNP: rs1324913238; hg19: chr14-105609158;