NM_006767.4(LZTR1):c.27del (p.Gln10fs) AND Noonan syndrome 10

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 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:: RCV003225720.10

Allele description [Variation Report for NM_006767.4(LZTR1):c.27del (p.Gln10fs)]

NM_006767.4(LZTR1):c.27del (p.Gln10fs)

Genes:

LOC130067016:ATAC-STARR-seq lymphoblastoid silent region 13504 [Gene]
LZTR1:leucine zipper like post translational regulator 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_006767.4(LZTR1):c.27del (p.Gln10fs)

HGVS:

NC_000022.11:g.20982398del
NG_034193.1:g.5130del
NM_006767.4:c.27delMANE SELECT
NP_006758.2:p.Gln10fs
LRG_989t1:c.27del
LRG_989:g.5130del
LRG_989p1:p.Gln10fs
NC_000022.10:g.21336681del
NC_000022.10:g.21336687del
NM_006767.3:c.27del
NM_006767.3:c.27delG
NM_006767.4:c.27delGMANE SELECT

Protein change:

Q10fs

Links:

OMIM: 600574.0004; dbSNP: rs587777613

NCBI 1000 Genomes Browser:

rs587777613

Molecular consequence:

NM_006767.4:c.27del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Noonan syndrome 10 (NS10)
Identifiers:: MONDO: MONDO:0014693; MedGen: C4225280; Orphanet: 648; OMIM: 616564

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003807996	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 23, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004175834	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003807996

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 23, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004175834

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 14, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV003807996.2

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

Description

ACMG classification criteria: PVS1 very strong, PS4 strong, PM2 supporting, PM3 moderated

#	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 Neuberg Centre For Genomic Medicine, NCGM, SCV004175834.1

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

Description

The frameshift c.27del(p.Gln10ArgfsTer15) variant in LZTR1 gene has been reported previously in heterozygous state in multiple individuals affected with LZTR1-related disorders (Johnston JJ, et. al., 2018; Smith MJ, et. al., 2015; Piotrowski A, et. al., 2014). The p.Gln10ArgfsTer15 variant has been reported with allele frequency of 0.006% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submissions). This variant causes a frameshift starting with codon Glutamine 10, changes this amino acid to Arginine residue, and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Gln10ArgfsTer15. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in this gene have been previously reported to be pathogenic (Bigenzahn JW, et. al., 2018; Steklov M, et. al., 2018). 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 22, 2024

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