NM_019032.6(ADAMTSL4):c.1786C>T (p.Gln596Ter) AND Isolated ectopia lentis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 10, 2014
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:: RCV004018319.1

Allele description [Variation Report for NM_019032.6(ADAMTSL4):c.1786C>T (p.Gln596Ter)]

NM_019032.6(ADAMTSL4):c.1786C>T (p.Gln596Ter)

Genes:

ADAMTSL4:ADAMTS like 4 [Gene - OMIM - HGNC]
ADAMTSL4-AS2:ADAMTSL4 antisense RNA 2 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.2

Genomic location:

Preferred name:

NM_019032.6(ADAMTSL4):c.1786C>T (p.Gln596Ter)

HGVS:

NC_000001.11:g.150556975C>T
NG_012172.1:g.12554C>T
NM_001288607.2:c.1855C>T
NM_001288608.2:c.1855C>T
NM_001378596.1:c.1786C>T
NM_019032.6:c.1786C>TMANE SELECT
NM_025008.5:c.1786C>T
NP_001275536.1:p.Gln619Ter
NP_001275537.1:p.Gln619Ter
NP_001365525.1:p.Gln596Ter
NP_061905.2:p.Gln596Ter
NP_079284.2:p.Gln596Ter
NC_000001.10:g.150529451C>T

Protein change:

Q596*

Molecular consequence:

NM_001288607.2:c.1855C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001288608.2:c.1855C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001378596.1:c.1786C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_019032.6:c.1786C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_025008.5:c.1786C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Isolated ectopia lentis (ECTOL1)
Identifiers:: MONDO: MONDO:0015998; MedGen: C1851286

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004847512	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 10, 2014)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19200529, 22736615, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004847512

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 10, 2014)

germline

clinical testing

PubMed (3)
[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 homozygous mutation in ADAMTSL4 causes autosomal-recessive isolated ectopia lentis.

Ahram D, Sato TS, Kohilan A, Tayeh M, Chen S, Leal S, Al-Salem M, El-Shanti H.

Am J Hum Genet. 2009 Feb;84(2):274-8. doi: 10.1016/j.ajhg.2009.01.007. Epub 2009 Feb 5.

PubMed [citation]

PMID:: 19200529
PMCID:: PMC2668005

A genotype-phenotype comparison of ADAMTSL4 and FBN1 in isolated ectopia lentis.

Chandra A, Aragon-Martin JA, Hughes K, Gati S, Reddy MA, Deshpande C, Cormack G, Child AH, Charteris DG, Arno G.

Invest Ophthalmol Vis Sci. 2012 Jul 24;53(8):4889-96. doi: 10.1167/iovs.12-9874.

PubMed [citation]

PMID:: 22736615

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847512.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The Gln596X variant in ADAMTSL4 has not been previously reported in individuals with isolated ectopia lentis or in large population studies. This nonsense variant leads to a premature termination codon at position 596, which is predicted to lead to a truncated or absent protein. Homozygous loss of function of the ADAMTSL4 gene has been descriebd as a cause of isolated ectopia lentis (Ahram 2009, Chandra 2012). In summary, this variant meets our criteria (http://pcpgm.partners.org/LMM) to be classified as pathogenic in a recessive manner for isolated ectopia lentis.

#	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 7, 2024

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