U.S. flag

An official website of the United States government

NM_032492.4(JAGN1):c.184C>T (p.Leu62Phe) AND Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 10, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001897076.6

Allele description [Variation Report for NM_032492.4(JAGN1):c.184C>T (p.Leu62Phe)]

NM_032492.4(JAGN1):c.184C>T (p.Leu62Phe)

Gene:
JAGN1:jagunal homolog 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p25.3
Genomic location:
Preferred name:
NM_032492.4(JAGN1):c.184C>T (p.Leu62Phe)
HGVS:
  • NC_000003.12:g.9893009C>T
  • NG_041779.1:g.7423C>T
  • NM_001363890.1:c.22C>T
  • NM_032492.4:c.184C>TMANE SELECT
  • NP_001350819.1:p.Leu8Phe
  • NP_115881.3:p.Leu62Phe
  • LRG_1228t1:c.184C>T
  • LRG_1228:g.7423C>T
  • LRG_1228p1:p.Leu62Phe
  • NC_000003.11:g.9934693C>T
Protein change:
L62F
Links:
dbSNP: rs768937406
NCBI 1000 Genomes Browser:
rs768937406
Molecular consequence:
  • NM_001363890.1:c.22C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032492.4:c.184C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Autosomal recessive severe congenital neutropenia due to JAGN1 deficiency
Synonyms:
Severe congenital neutropenia 6, autosomal recessive
Identifiers:
MONDO: MONDO:0014456; MedGen: C4014954; Orphanet: 423384; OMIM: 616022

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002169056Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 10, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002169056.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant is present in population databases (rs768937406, ExAC 0.01%). This sequence change replaces leucine with phenylalanine at codon 62 of the JAGN1 protein (p.Leu62Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant has not been reported in the literature in individuals with JAGN1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024