NM_213599.3(ANO5):c.2273_2280dup (p.Tyr761delinsValTer) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 19, 2023
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:: RCV003800547.2

Allele description [Variation Report for NM_213599.3(ANO5):c.2273_2280dup (p.Tyr761delinsValTer)]

NM_213599.3(ANO5):c.2273_2280dup (p.Tyr761delinsValTer)

Gene:

ANO5:anoctamin 5 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11p14.3

Genomic location:

Preferred name:

NM_213599.3(ANO5):c.2273_2280dup (p.Tyr761delinsValTer)

HGVS:

NC_000011.10:g.22274606_22274613dup
NG_015844.1:g.86431_86438dup
NM_001142649.2:c.2270_2277dup
NM_001410963.1:c.2231_2238dup
NM_001410964.1:c.2228_2235dup
NM_213599.3:c.2273_2280dupMANE SELECT
NP_001136121.1:p.Tyr760delinsValTer
NP_001397892.1:p.Tyr747delinsValTer
NP_001397893.1:p.Tyr746delinsValTer
NP_998764.1:p.Tyr761Valfs
NP_998764.1:p.Tyr761delinsValTer
LRG_868t1:c.2273_2280dup
LRG_868:g.86431_86438dup
LRG_868p1:p.Tyr761Valfs
NC_000011.9:g.22296151_22296152insGTCTAGTT
NC_000011.9:g.22296152_22296159dup
NM_213599.2:c.2273_2280dup

Molecular consequence:

NM_001142649.2:c.2270_2277dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001410963.1:c.2231_2238dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001410964.1:c.2228_2235dup - nonsense - [Sequence Ontology: SO:0001587]
NM_213599.3:c.2273_2280dup - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004589266	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 19, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21186264, 23606453, 25891276, 30919934, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004589266

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 19, 2023)

germline

clinical testing

PubMed (5)
[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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004589266.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with ANO5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr761Valfs*2) 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).

#	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: Sep 29, 2024

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