NM_213599.3(ANO5):c.2004del (p.Leu669fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 7, 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:: RCV000700782.6

Allele description [Variation Report for NM_213599.3(ANO5):c.2004del (p.Leu669fs)]

NM_213599.3(ANO5):c.2004del (p.Leu669fs)

Gene:

ANO5:anoctamin 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p14.3

Genomic location:

Preferred name:

NM_213599.3(ANO5):c.2004del (p.Leu669fs)

HGVS:

NC_000011.10:g.22270417del
NG_015844.1:g.82242del
NM_001142649.2:c.2001del
NM_213599.3:c.2004delMANE SELECT
NP_001136121.1:p.Leu668fs
NP_998764.1:p.Leu669fs
LRG_868t1:c.2004del
LRG_868:g.82242del
NC_000011.9:g.22291961del
NC_000011.9:g.22291963del
NM_213599.2:c.2004del
NM_213599.2:c.2004delG
NM_213599.3:c.2004delGMANE SELECT

Protein change:

L668fs

Links:

dbSNP: rs886043172

NCBI 1000 Genomes Browser:

rs886043172

Molecular consequence:

NM_001142649.2:c.2001del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_213599.3:c.2004del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Gnathodiaphyseal dysplasia (GDD)
Synonyms:: GNATHODIAPHYSEAL SCLEROSIS; OSTEOGENESIS IMPERFECTA WITH UNUSUAL SKELETAL LESIONS; Osteogenesis imperfecta Levin type; 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000829553	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 7, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21186264, 23606453, 25891276, 30919934, 23663589, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000829553

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 7, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy.

Hicks D, Sarkozy A, Muelas N, Köehler K, Huebner A, Hudson G, Chinnery PF, Barresi R, Eagle M, Polvikoski T, Bailey G, Miller J, Radunovic A, Hughes PJ, Roberts R, Krause S, Walter MC, Laval SH, Straub V, Lochmüller H, Bushby K.

Brain. 2011 Jan;134(Pt 1):171-182. doi: 10.1093/brain/awq294.

PubMed [citation]

PMID:: 21186264
PMCID:: PMC4038512

ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation.

Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, Deschauer M, Harris E, Rufibach L, Hwang E, Bashir R, Walter MC, Krause S, van den Bergh P, Illa I, Pénisson-Besnier I, De Waele L, Turnbull D, Guglieri M, Schrank B, Schoser B, Seeger J, et al.

Hum Mutat. 2013 Aug;34(8):1111-8. doi: 10.1002/humu.22342. Epub 2013 Jun 12.

PubMed [citation]

PMID:: 23606453

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000829553.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Leu669Phefs*6) in the ANO5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276, 30919934). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with ANO5-related muscular dystrophy (PMID: 23663589). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 285669). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 13, 2025

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