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NM_213599.3(ANO5):c.1563G>T (p.Leu521Phe) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 26, 2024
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:
RCV000703928.8

Allele description [Variation Report for NM_213599.3(ANO5):c.1563G>T (p.Leu521Phe)]

NM_213599.3(ANO5):c.1563G>T (p.Leu521Phe)

Gene:
ANO5:anoctamin 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p14.3
Genomic location:
Preferred name:
NM_213599.3(ANO5):c.1563G>T (p.Leu521Phe)
HGVS:
  • NC_000011.10:g.22259674G>T
  • NG_015844.1:g.71499G>T
  • NM_001142649.2:c.1560G>T
  • NM_213599.3:c.1563G>TMANE SELECT
  • NP_001136121.1:p.Leu520Phe
  • NP_998764.1:p.Leu521Phe
  • NP_998764.1:p.Leu521Phe
  • LRG_868t1:c.1563G>T
  • LRG_868:g.71499G>T
  • LRG_868p1:p.Leu521Phe
  • NC_000011.9:g.22281220G>T
  • NM_213599.2:c.1563G>T
Protein change:
L520F
Links:
dbSNP: rs190937193
NCBI 1000 Genomes Browser:
rs190937193
Molecular consequence:
  • NM_001142649.2:c.1560G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_213599.3:c.1563G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Gnathodiaphyseal dysplasia (GDD)
Synonyms:
GNATHODIAPHYSEAL SCLEROSIS; Osteogenesis imperfecta Levin type; Levin syndrome 2; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008151; MedGen: C1833736; OMIM: 166260
Name:
Autosomal recessive limb-girdle muscular dystrophy type 2L (LGMDR12)
Synonyms:
Limb-girdle muscular dystrophy, type 2L; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 12
Identifiers:
MONDO: MONDO:0012652; MedGen: C1969785; Orphanet: 206549; OMIM: 611307

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000832855Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 26, 2024) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.

Nallamilli BRR, Chakravorty S, Kesari A, Tanner A, Ankala A, Schneider T, da Silva C, Beadling R, Alexander JJ, Askree SH, Whitt Z, Bean L, Collins C, Khadilkar S, Gaitonde P, Dastur R, Wicklund M, Mozaffar T, Harms M, Rufibach L, Mittal P, Hegde M.

Ann Clin Transl Neurol. 2018 Dec;5(12):1574-1587. doi: 10.1002/acn3.649.

PubMed [citation]
PMID:
30564623
PMCID:
PMC6292381

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, SCV000832855.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 521 of the ANO5 protein (p.Leu521Phe). This variant is present in population databases (rs190937193, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of ANO5-related conditions (PMID: 30564623). ClinVar contains an entry for this variant (Variation ID: 282165). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ANO5 protein function with a negative predictive value of 95%. 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.

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

Last Updated: Sep 29, 2024