NM_019032.6(ADAMTSL4):c.2008C>T (p.Arg670Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 14, 2023
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:: RCV001731326.6

Allele description [Variation Report for NM_019032.6(ADAMTSL4):c.2008C>T (p.Arg670Ter)]

NM_019032.6(ADAMTSL4):c.2008C>T (p.Arg670Ter)

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.2008C>T (p.Arg670Ter)

HGVS:

NC_000001.11:g.150557296C>T
NG_012172.1:g.12875C>T
NM_001288607.2:c.1891C>T
NM_001288608.2:c.2077C>T
NM_001378596.1:c.2008C>T
NM_019032.6:c.2008C>TMANE SELECT
NM_025008.5:c.2008C>T
NP_001275536.1:p.Arg631Ter
NP_001275537.1:p.Arg693Ter
NP_001365525.1:p.Arg670Ter
NP_061905.2:p.Arg670Ter
NP_079284.2:p.Arg670Ter
NC_000001.10:g.150529772C>T
NM_019032.5:c.2008C>T

Protein change:

R631*; ARG670TER

Links:

OMIM: 610113.0005; dbSNP: rs368482584

NCBI 1000 Genomes Browser:

rs368482584

Molecular consequence:

NM_001288607.2:c.1891C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001288608.2:c.2077C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001378596.1:c.2008C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_019032.6:c.2008C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_025008.5:c.2008C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Progressive muscular atrophy
Progressive muscular atrophy

MedGen
C0917981[conceptid] (1)
MedGen
Autoimmune polyendocrinopathy
Autoimmune polyendocrinopathy

MedGen
C0085409[conceptid] (1)
MedGen

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001982365	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 6, 2021)	germline	clinical testing	Citation Link,
SCV002228416	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 14, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28642162, 20564469, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001982365

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 6, 2021)

germline

clinical testing

Citation Link,

SCV002228416

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 14, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield.

Overwater E, Floor K, van Beek D, de Boer K, van Dijk T, Hilhorst-Hofstee Y, Hoogeboom AJM, van Kaam KJ, van de Kamp JM, Kempers M, Krapels IPC, Kroes HY, Loeys B, Salemink S, Stumpel CTRM, Verhoeven VJM, Wijnands-van den Berg E, Cobben JM, van Tintelen JP, Weiss MM, Houweling AC, Maugeri A.

Eur J Med Genet. 2017 Sep;60(9):465-473. doi: 10.1016/j.ejmg.2017.06.005. Epub 2017 Jun 19.

PubMed [citation]

PMID:: 28642162

Role of ADAMTSL4 mutations in FBN1 mutation-negative ectopia lentis patients.

Aragon-Martin JA, Ahnood D, Charteris DG, Saggar A, Nischal KK, Comeglio P, Chandra A, Child AH, Arno G.

Hum Mutat. 2010 Aug;31(8):E1622-31. doi: 10.1002/humu.21305.

PubMed [citation]

PMID:: 20564469

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV001982365.2

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 27535533, 20564469, 31589614)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002228416.3

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

Description

This sequence change creates a premature translational stop signal (p.Arg670*) in the ADAMTSL4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADAMTSL4 are known to be pathogenic (PMID: 20564469, 28642162). This variant is present in population databases (rs368482584, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with ectopia lentis (PMID: 20564469). ClinVar contains an entry for this variant (Variation ID: 39557). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine