NM_019032.6(ADAMTSL4):c.1774G>A (p.Gly592Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV001908836.4

Allele description [Variation Report for NM_019032.6(ADAMTSL4):c.1774G>A (p.Gly592Ser)]

NM_019032.6(ADAMTSL4):c.1774G>A (p.Gly592Ser)

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.1774G>A (p.Gly592Ser)

HGVS:

NC_000001.11:g.150556963G>A
NG_012172.1:g.12542G>A
NM_001288607.2:c.1843G>A
NM_001288608.2:c.1843G>A
NM_001378596.1:c.1774G>A
NM_019032.6:c.1774G>AMANE SELECT
NM_025008.5:c.1774G>A
NP_001275536.1:p.Gly615Ser
NP_001275537.1:p.Gly615Ser
NP_001365525.1:p.Gly592Ser
NP_061905.2:p.Gly592Ser
NP_079284.2:p.Gly592Ser
NC_000001.10:g.150529439G>A

Protein change:

G592S

Links:

dbSNP: rs1001450254

NCBI 1000 Genomes Browser:

rs1001450254

Molecular consequence:

NM_001288607.2:c.1843G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001288608.2:c.1843G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378596.1:c.1774G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_019032.6:c.1774G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_025008.5:c.1774G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Microbe sample from Brevibacillus brevis
Microbe sample from Brevibacillus brevis

biosample
probable Family 9 glycosyl hydrolase [Sporisorium reilianum SRZ2]
probable Family 9 glycosyl hydrolase [Sporisorium reilianum SRZ2]
gi|323508199|emb|CBQ68070.1|

Protein
Verrucomicrobia bacterium SCGC AC-312-P03
Verrucomicrobia bacterium SCGC AC-312-P03
Verrucomicrobia bacterium SCGC AC-312-P03 Genome sequencing

BioProject

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
SCV002174205	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25975359, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002174205

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 2024)

germline

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

Citations

PubMed

ADAMTSL4-associated isolated ectopia lentis: Further patients, novel mutations and a detailed phenotype description.

Neuhann TM, Stegerer A, Riess A, Blair E, Martin T, Wieser S, Kläs R, Bouman A, Kuechler A, Rittinger O.

Am J Med Genet A. 2015 Oct;167A(10):2376-81. doi: 10.1002/ajmg.a.37157. Epub 2015 May 14.

PubMed [citation]

PMID:: 25975359

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002174205.3

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 592 of the ADAMTSL4 protein (p.Gly592Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ectopia lentis (PMID: 25975359). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1403030). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ADAMTSL4 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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