JAGN1 p.Leu90Leu

Variant names:

• chr3-9893092-T-T
• NM_032492.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr3-9893093--
• chr3-9893095-C-T
• chr3-9893095-C-A
• chr3-9893095-C-G
• chr3-9893093-CTC-TTA
• chr3-9893093-CTC-TTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032492.4(JAGN1):​c. variant causes a exon region 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: 32)
• Consequence: JAGN1 NM_032492.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• Publications: 0 publications found

Genes affected

JAGN1 (HGNC:26926): (jagunal homolog 1) The protein encoded by this gene is a transmembrane protein. It functions in the early secretory pathway and is necessary for neutrophil differentiation and survival. Mutations in this gene result in severe congenital neutropenia. [provided by RefSeq, Oct 2014]

JAGN1 Gene-Disease associations (from GenCC):

• autosomal recessive severe congenital neutropenia due to JAGN1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032492.4. 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
	JAGN1	NM_032492.4	MANE Select	c.		exon_region	Exon 2 of 2	NP_115881.3
	JAGN1	NM_001363890.1		c.		exon_region	Exon 2 of 2	NP_001350819.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.98

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: chr3-9934776;