dbSNP rs587632836: JAG2:p.Leu16_Leu17del (chr14-105168369-CCAGCAG-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_002226.5(JAG2):c.46_51delCTGCTG(p.Leu16_Leu17del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 866,480 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: not found (cov: 30)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

JAG2
NM_002226.5 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

muscular dystrophy, limb-girdle, autosomal recessive 27
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

JAG2 links:

ENSG00000257622 (HGNC:):

ENSG00000257622 links:

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ACMG classification

Classification was made for transcript

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAG2	NM_002226.5	MANE Select	c.46_51delCTGCTG	p.Leu16_Leu17del	conservative_inframe_deletion	Exon 1 of 26	NP_002217.3
	JAG2	NM_145159.3		c.46_51delCTGCTG	p.Leu16_Leu17del	conservative_inframe_deletion	Exon 1 of 25	NP_660142.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
JAG2	ENST00000331782.8	TSL:1 MANE Select	c.46_51delCTGCTG	p.Leu16_Leu17del	conservative_inframe_deletion	Exon 1 of 26	ENSP00000328169.3
JAG2	ENST00000347004.2	TSL:1	c.46_51delCTGCTG	p.Leu16_Leu17del	conservative_inframe_deletion	Exon 1 of 25	ENSP00000328566.2
ENSG00000257622	ENST00000548203.1	TSL:3	n.67-10612_67-10607delCTGCTG		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000231

AC:

AN:

866480

Hom.:

AF XY:

0.00000239

AC XY:

AN XY:

418328

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

16338

American (AMR)

AF:

0.00

AC:

AN:

10276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9424

East Asian (EAS)

AF:

0.00

AC:

AN:

4384

South Asian (SAS)

AF:

0.00

AC:

AN:

36098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1884

European-Non Finnish (NFE)

AF:

0.00000265

AC:

AN:

754820

Other (OTH)

AF:

0.00

AC:

AN:

29118

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over