NM_213599.3(ANO5):c.2521C>G (p.His841Asp) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Sep 7, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000176339.14

Allele description [Variation Report for NM_213599.3(ANO5):c.2521C>G (p.His841Asp)]

NM_213599.3(ANO5):c.2521C>G (p.His841Asp)

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.2521C>G (p.His841Asp)

HGVS:

NC_000011.10:g.22279544C>G
NG_015844.1:g.91369C>G
NM_001142649.2:c.2518C>G
NM_213599.3:c.2521C>GMANE SELECT
NP_001136121.1:p.His840Asp
NP_998764.1:p.His841Asp
NP_998764.1:p.His841Asp
LRG_868t1:c.2521C>G
LRG_868:g.91369C>G
LRG_868p1:p.His841Asp
NC_000011.9:g.22301090C>G
NC_000011.9:g.22301090C>G
NM_213599.2(ANO5):c.2521C>G
NM_213599.2:c.2521C>G
p.His841Asp

Protein change:

H840D

Links:

dbSNP: rs781027702

NCBI 1000 Genomes Browser:

rs781027702

Molecular consequence:

NM_001142649.2:c.2518C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_213599.3:c.2521C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329068	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jul 7, 2015)	germline	clinical testing	Citation Link,
SCV000331780	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Likely pathogenic (Sep 1, 2016)	germline	clinical testing	Citation Link,
SCV002021396	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002771484	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Jul 20, 2021)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 31395899, 23606453, 32403337, 24022920, 32528171, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	7	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure.

Jarmula A, Łusakowska A, Fichna JP, Topolewska M, Macias A, Johnson K, Töpf A, Straub V, Rosiak E, Szczepaniak K, Dunin-Horkawicz S, Maruszak A, Kaminska AM, Redowicz MJ.

Sci Rep. 2019 Aug 8;9(1):11533. doi: 10.1038/s41598-019-47849-3.

PubMed [citation]

PMID:: 31395899
PMCID:: PMC6687736

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000329068.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The H841D missense variant in the ANO5 gene has been reported previously in an individual with limb-girdle muscular dystrophy type 2L also known as, anoctaminopathy, who was heterozygous for this change and did not have another identifiable variant (Sarkozy et al., 2013). H841D was subsequently identified in an individual with limb-girdle muscular dystrophy type 2L who was compound heterozygous for H841D and another ANO5 variant(Leung et al., 2014). The H841D pathogenic variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in silico analysis predicts this sequence change is probably damaging to the protein structure/function, and other missense variants in nearby residues (M833K, M839R) have been reported in the Human Gene Mutation Database in association with ANO5-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Given the available evidence, we interpret H841D as a pathogenic variant.

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

From Eurofins Ntd Llc (ga), SCV000331780.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	not provided

#	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		7	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002021396.3

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

#	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

From Athena Diagnostics, SCV002771484.1

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

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant segregates with disease in at least one family. Computational tools predict that this variant is damaging.

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

Last Updated: Apr 13, 2025

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