NM_213599.3(ANO5):c.191dup (p.Asn64fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 30, 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:: RCV000627781.11

Allele description [Variation Report for NM_213599.3(ANO5):c.191dup (p.Asn64fs)]

NM_213599.3(ANO5):c.191dup (p.Asn64fs)

Gene:

ANO5:anoctamin 5 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11p14.3

Genomic location:

Preferred name:

NM_213599.3(ANO5):c.191dup (p.Asn64fs)

HGVS:

NC_000011.10:g.22221107dup
NG_015844.1:g.32932dup
NM_001142649.2:c.188dup
NM_213599.3:c.191dupMANE SELECT
NP_001136121.1:p.Asn63fs
NP_998764.1:p.Asn64fs
LRG_868:g.32932dup
NC_000011.10:g.22221100_22221101insA
NC_000011.9:g.22242646_22242647insA
NC_000011.9:g.22242653dup
NM_001142649.1:c.188dupA
NM_213599.2:c.191dupA
NM_213599.3:c.191dup
NM_213599.3:c.191dupAMANE SELECT
p.(Asn64Lysfs*15)
p.Asn64LysfsTer15

Protein change:

N63fs

Links:

OMIM: 608662.0004; dbSNP: rs137854521

NCBI 1000 Genomes Browser:

rs137854521

Molecular consequence:

NM_001142649.2:c.188dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_213599.3:c.191dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000645880	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 30, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 30919934, 23606453, 25891276, 20096397, 21186264, 21739273, 23607914, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000645880

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 30, 2024)

germline

clinical testing

PubMed (8)
[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

Autosomal recessive limb-girdle and Miyoshi muscular dystrophies in the Netherlands: The clinical and molecular spectrum of 244 patients.

Ten Dam L, Frankhuizen WS, Linssen WHJP, Straathof CS, Niks EH, Faber K, Fock A, Kuks JB, Brusse E, de Coo R, Voermans N, Verrips A, Hoogendijk JE, van der Pol L, Westra D, de Visser M, van der Kooi AJ, Ginjaar I.

Clin Genet. 2019 Aug;96(2):126-133. doi: 10.1111/cge.13544. Epub 2019 May 6.

PubMed [citation]

PMID:: 30919934

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 (8)

Details of each submission

From Invitae, SCV000645880.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Asn64Lysfs*15) 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 (rs575136178, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This premature translational stop signal has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy 2L (LGMD2L) and ANO5-related conditions (PMID: 20096397, 21186264, 21739273, 23606453, 23607914, 25891276). It is commonly reported in individuals of Northern European ancestry (PMID: 20096397, 21186264, 21739273, 23607914). ClinVar contains an entry for this variant (Variation ID: 2164). 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: Jun 2, 2024

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