U.S. flag

An official website of the United States government

NM_001289808.2(CRYAB):c.32G>A (p.Arg11His) AND Cataract 16 multiple types

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 24, 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:
RCV004789399.1

Allele description [Variation Report for NM_001289808.2(CRYAB):c.32G>A (p.Arg11His)]

NM_001289808.2(CRYAB):c.32G>A (p.Arg11His)

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.32G>A (p.Arg11His)
HGVS:
  • NC_000011.10:g.111911693C>T
  • NG_009824.3:g.17030G>A
  • NG_033080.2:g.3958C>T
  • NM_001289807.1:c.32G>A
  • NM_001289808.2:c.32G>AMANE SELECT
  • NM_001368245.1:c.32G>A
  • NM_001885.3:c.32G>A
  • NP_001276736.1:p.Arg11His
  • NP_001276737.1:p.Arg11His
  • NP_001355174.1:p.Arg11His
  • NP_001876.1:p.Arg11His
  • LRG_407t1:c.32G>A
  • LRG_407t2:c.32G>A
  • LRG_407:g.17030G>A
  • LRG_407p1:p.Arg11His
  • LRG_407p2:p.Arg11His
  • NC_000011.9:g.111782417C>T
  • NG_009824.2:g.17030G>A
  • NG_033080.1:g.3958C>T
  • NM_001885.1:c.32G>A
  • NM_001885.2:c.32G>A
Protein change:
R11H
Links:
dbSNP: rs782809283
NCBI 1000 Genomes Browser:
rs782809283
Molecular consequence:
  • NM_001289807.1:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289808.2:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368245.1:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001885.3:c.32G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cataract 16 multiple types
Synonyms:
CATARACT 16, POSTERIOR POLAR; CATARACT 16, CONGENITAL LAMELLAR; CATARACT, CONGENITAL LAMELLAR
Identifiers:
MONDO: MONDO:0013411; MedGen: C3808377; Orphanet: 91492; Orphanet: 98992; Orphanet: 98993; Orphanet: 98995; OMIM: 613763

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001244993Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jun 24, 2022) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A novel alphaB-crystallin mutation associated with autosomal dominant congenital lamellar cataract.

Liu Y, Zhang X, Luo L, Wu M, Zeng R, Cheng G, Hu B, Liu B, Liang JJ, Shang F.

Invest Ophthalmol Vis Sci. 2006 Mar;47(3):1069-75.

PubMed [citation]
PMID:
16505043
PMCID:
PMC2078606

A novel mutation in CRYAB associated with autosomal dominant congenital nuclear cataract in a Chinese family.

Chen Q, Ma J, Yan M, Mothobi ME, Liu Y, Zheng F.

Mol Vis. 2009 Jul 10;15:1359-65.

PubMed [citation]
PMID:
19597569
PMCID:
PMC2709425
See all PubMed Citations (9)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV001244993.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0104 - Dominant negative is a known mechanism of disease in this gene and is associated with dominant cataracts (MIM#613763) (PMID: 31239701, 16505043). LoF is a speculated mechanism for other conditions (DECIPHER). (I) 0108 - This gene is associated with both recessive and dominant disease. This gene is associated with both dominant and recessive cataract 16, multiple types (MIM#613763) and dominant myofibrillar myopathy 2 (MIM#608810). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to histidine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a condition (8 heterozygotes, 0 homozygotes). (SP) 0309 - Two alternative amino acid changes at the same position have been observed in gnomAD (v2) (highest allele: 7 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by two in silico tools and highly conserved with a minor amino acid change. (SP) 0600 - Variant is located in the annotated Crystallin domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0803 - This variant has limited previous evidence of pathogenicity in one family with autosomal dominant congenital nuclear cataract (PMID: 19597569). This variant has been listed as a VUS in a hypertrophic cardiomyopathy cohort (PMID: 30531895). This variant has also been reported as likely pathogenic and VUS in ClinVar. (SP) 0903 - This variant has limited evidence for segregation with disease in one family with autosomal dominant congenital nuclear cataract (PMID: 19597569). (SP) 1010 - Functional evidence for this variant is inconclusive. Functional studies showed the mutant protein altered protein structure and activity, promoted apoptosis (PMID: 21087083), showed moderate number of cells with aggregates (PMID: 23194663) and formed smaller oligomers than WT protein (PMID: 32533979). However, mutant protein did not affect the capability of alphaB-crystalllin in enhacing the sodium current density (PMID: 26961874). (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 28, 2025