rs587632836

chr14-105168369-CCAG-Cchr14-105168369-CCAG-CCAGCAGchr14-105168369-CCAG-CCAGCAGCAG

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_002226.5(JAG2):c.49_51del(p.Leu17del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 985,194 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: JAG2 NM_002226.5 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002226.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAG2	NM_002226.5	c.49_51del	p.Leu17del	inframe_deletion	1/26	ENST00000331782.8
JAG2	NM_145159.3	c.49_51del	p.Leu17del	inframe_deletion	1/25
JAG2	XM_047431354.1	c.49_51del	p.Leu17del	inframe_deletion	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAG2	ENST00000331782.8	c.49_51del	p.Leu17del	inframe_deletion	1/26	1	NM_002226.5	P1
JAG2	ENST00000347004.2	c.49_51del	p.Leu17del	inframe_deletion	1/25	1

Frequencies

GnomAD3 genomes AF: 0.00000687 AC: 1 AN: 145654 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00350 AC: 2938 AN: 839452 Hom.: 0 AF XY: 0.00377 AC XY: 1525 AN XY: 404600

Gnomad4 AFR exome AF: 0.00341

Gnomad4 AMR exome AF: 0.0120

Gnomad4 ASJ exome AF: 0.00691

Gnomad4 EAS exome AF: 0.00405

Gnomad4 SAS exome AF: 0.00874

Gnomad4 FIN exome AF: 0.00866

Gnomad4 NFE exome AF: 0.00307

Gnomad4 OTH exome AF: 0.00379

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145742 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 70932

Gnomad4 AFR AF: 0.0000246

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs587632836; hg19: chr14-105634706;