NM_001289808.2(CRYAB):c.514del (p.Ala172fs) AND Myofibrillar myopathy 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 17, 2019
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:: RCV001175167.2

Allele description [Variation Report for NM_001289808.2(CRYAB):c.514del (p.Ala172fs)]

NM_001289808.2(CRYAB):c.514del (p.Ala172fs)

Gene:

CRYAB:crystallin alpha B [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q23.1

Genomic location:

Preferred name:

NM_001289808.2(CRYAB):c.514del (p.Ala172fs)

HGVS:

NC_000011.10:g.111908778del
NG_009824.3:g.19945del
NG_033080.2:g.1043del
NM_001289807.1:c.514del
NM_001289808.2:c.514delMANE SELECT
NM_001330379.1:c.313del
NM_001368245.1:c.514del
NM_001368246.1:c.313del
NM_001885.3:c.514del
NP_001276736.1:p.Ala172fs
NP_001276737.1:p.Ala172fs
NP_001317308.1:p.Ala105fs
NP_001355174.1:p.Ala172fs
NP_001355175.1:p.Ala105fs
NP_001876.1:p.Ala172fs
LRG_407t1:c.514del
LRG_407t2:c.514del
LRG_407:g.19945del
LRG_407p1:p.Ala172fs
LRG_407p2:p.Ala172fs
NC_000011.9:g.111779502del
NG_009824.2:g.19945del
NG_033080.1:g.1043del
NM_001885.2:c.514delG

Protein change:

A105fs

Links:

dbSNP: rs1965352990

NCBI 1000 Genomes Browser:

rs1965352990

Molecular consequence:

NM_001289807.1:c.514del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289808.2:c.514del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330379.1:c.313del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368245.1:c.514del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001368246.1:c.313del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001885.3:c.514del - frameshift variant - [Sequence Ontology: SO:0001589]

Functional consequence:

C-terminal protein elongation [Variation Ontology: 0125]

Observations:

Condition(s)

Name:: Myofibrillar myopathy 2
Synonyms:: MYOPATHY, DESMIN-RELATED, ASSOCIATED WITH MUTATION IN THE CRYAB GENE; MYOPATHY, MYOFIBRILLAR, ALPHA-B CRYSTALLIN-RELATED; Alpha-B crystallinopathy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012130; MedGen: C1837317; Orphanet: 280553; OMIM: 608810

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001132042	Genetics, INEBIR	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 17, 2019)	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32420686, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001132042

Genetics, INEBIR

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 17, 2019)

de novo

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
Caucasian	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel dominant mutation in CRYAB gene leading to a severe phenotype with childhood onset.

Marcos AT, Amorós D, Muñoz-Cabello B, Galán F, Rivas Infante E, Alcaraz-Mas L, Navarro-Pando JM.

Mol Genet Genomic Med. 2020 Aug;8(8):e1290. doi: 10.1002/mgg3.1290. Epub 2020 May 18.

PubMed [citation]

PMID:: 32420686
PMCID:: PMC7434720

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

Details of each submission

From Genetics, INEBIR, SCV001132042.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	1	not provided	not provided	clinical testing	PubMed (2)

Description

The c.514delG p.(Ala172fs) de novo variant in CRYAB has been detected in a Spanish boy with autosomal dominant congenite bilateral cataracts, palpebral bilateral ptosis, congenital hypotonia, dysfunction of the mitochondrial respiratory chain and a slight delay in motor skills acquisition, acute respiratory failure, he has a permanent tracheostomy for intermittent mechanical respiratory assistance and also presented dysphagia, since then he is basically fed by gastrostomy. Cardiomyopathy was not observed at the age of 4 years old.

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

Last Updated: Apr 6, 2024

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