NM_001289808.2(CRYAB):c.325-2A>G AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 13, 2022
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:: RCV002444476.2

Allele description [Variation Report for NM_001289808.2(CRYAB):c.325-2A>G]

NM_001289808.2(CRYAB):c.325-2A>G

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.1

Genomic location:

Preferred name:

NM_001289808.2(CRYAB):c.325-2A>G

HGVS:

NC_000011.10:g.111908969T>C
NG_009824.3:g.19754A>G
NG_033080.2:g.1234T>C
NM_001289807.1:c.325-2A>G
NM_001289808.2:c.325-2A>GMANE SELECT
NM_001330379.1:c.124-2A>G
NM_001368245.1:c.325-2A>G
NM_001368246.1:c.124-2A>G
NM_001885.3:c.325-2A>G
LRG_407t1:c.325-2A>G
LRG_407t2:c.325-2A>G
LRG_407:g.19754A>G
NC_000011.9:g.111779693T>C
NM_001885.1:c.325-2A>G
NM_001885.2:c.325-2A>G
c.325-2A>G

Links:

dbSNP: rs202024436

NCBI 1000 Genomes Browser:

rs202024436

Molecular consequence:

NM_001289807.1:c.325-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001289808.2:c.325-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001330379.1:c.124-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001368245.1:c.325-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001368246.1:c.124-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001885.3:c.325-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002612431	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29544605, 33906374 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002612431

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 13, 2022)

germline

clinical testing

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

Citation Link

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

Cardiac Genetic Predisposition in Sudden Infant Death Syndrome.

Tester DJ, Wong LCH, Chanana P, Jaye A, Evans JM, FitzPatrick DR, Evans MJ, Fleming P, Jeffrey I, Cohen MC, Tfelt-Hansen J, Simpson MA, Behr ER, Ackerman MJ.

J Am Coll Cardiol. 2018 Mar 20;71(11):1217-1227. doi: 10.1016/j.jacc.2018.01.030.

PubMed [citation]

PMID:: 29544605

Genetic Causes of Cardiomyopathy in Children: First Results From the Pediatric Cardiomyopathy Genes Study.

Ware SM, Wilkinson JD, Tariq M, Schubert JA, Sridhar A, Colan SD, Shi L, Canter CE, Hsu DT, Webber SA, Dodd DA, Everitt MD, Kantor PF, Addonizio LJ, Jefferies JL, Rossano JW, Pahl E, Rusconi P, Chung WK, Lee T, Towbin JA, Lal AK, et al.

J Am Heart Assoc. 2021 May 4;10(9):e017731. doi: 10.1161/JAHA.120.017731. Epub 2021 Apr 28. Erratum in: J Am Heart Assoc. 2021 Jun;10(11):e020840.

PubMed [citation]

PMID:: 33906374
PMCID:: PMC8200745

Details of each submission

From Ambry Genetics, SCV002612431.2

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

Description

The c.325-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 3 in the CRYAB gene. This variant has been detected in a victim of sudden infant death and in an individual with hypertrophic cardiomyopathy (Tester DJ et al. J Am Coll Cardiol, 2018 03;71:1217-1227; Ware SM et al. J Am Heart Assoc, 2021 05;10:e017731). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and may result in the creation or strengthening of a novel splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, this alteration occurs at the 3' terminus of the CRYAB gene and is not expected to trigger nonsense-mediated mRNA decay. The exact functional effect of this alteration is unknown. In addition, loss of function of CRYAB has not been established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 1, 2024

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