14-105168369-CCAGCAG-CCAGCAGCAGCAG

Variant names:

• chr14-105168374-A-AGCAGCA
• NM_002226.5:c.41_46dupTGCTGC

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_002226.5(JAG2):​c.41_46dupTGCTGC​(p.Leu15_Leu16dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: JAG2 NM_002226.5 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• muscular dystrophy, limb-girdle, autosomal recessive 27

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000257622 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002226.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002226.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAG2	NM_002226.5	MANE Select	c.41_46dupTGCTGC	p.Leu15_Leu16dup	conservative_inframe_insertion	Exon 1 of 26	NP_002217.3
	JAG2	NM_145159.3		c.41_46dupTGCTGC	p.Leu15_Leu16dup	conservative_inframe_insertion	Exon 1 of 25	NP_660142.1	Q9Y219-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAG2	ENST00000331782.8	TSL:1 MANE Select	c.41_46dupTGCTGC	p.Leu15_Leu16dup	conservative_inframe_insertion	Exon 1 of 26	ENSP00000328169.3	Q9Y219-1
	JAG2	ENST00000347004.2	TSL:1	c.41_46dupTGCTGC	p.Leu15_Leu16dup	conservative_inframe_insertion	Exon 1 of 25	ENSP00000328566.2	Q9Y219-2
	JAG2	ENST00000938643.1		c.41_46dupTGCTGC	p.Leu15_Leu16dup	conservative_inframe_insertion	Exon 1 of 26	ENSP00000608702.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 14

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.010

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-105634711;