NM_015443.4(KANSL1):c.1042C>T (p.Arg348Ter) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 5, 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:: RCV000622541.4

Allele description [Variation Report for NM_015443.4(KANSL1):c.1042C>T (p.Arg348Ter)]

NM_015443.4(KANSL1):c.1042C>T (p.Arg348Ter)

Gene:

KANSL1:KAT8 regulatory NSL complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_015443.4(KANSL1):c.1042C>T (p.Arg348Ter)

HGVS:

NC_000017.11:g.46171102G>A
NG_032784.1:g.59273C>T
NM_001193465.2:c.1042C>T
NM_001193466.2:c.1042C>T
NM_001379198.1:c.1042C>T
NM_015443.4:c.1042C>TMANE SELECT
NP_001180394.1:p.Arg348Ter
NP_001180394.1:p.Arg348Ter
NP_001180395.1:p.Arg348Ter
NP_001366127.1:p.Arg348Ter
NP_056258.1:p.Arg348Ter
NC_000017.10:g.44248468G>A
NM_001193465.1:c.1042C>T
NM_001193466.1:c.1042C>T
NM_001193466.2:c.1042C>T

Protein change:

R348*

Links:

dbSNP: rs1427624649

NCBI 1000 Genomes Browser:

rs1427624649

Molecular consequence:

NM_001193465.2:c.1042C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001193466.2:c.1042C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001379198.1:c.1042C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015443.4:c.1042C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

Recent activity

Clear Turn Off Turn On

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
SCV000742382	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Apr 5, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26424144, 32371413, 36529818 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000742382

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Apr 5, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype-phenotype correlations in a large cohort of patients.

Zollino M, Marangi G, Ponzi E, Orteschi D, Ricciardi S, Lattante S, Murdolo M, Battaglia D, Contaldo I, Mercuri E, Stefanini MC, Caumes R, Edery P, Rossi M, Piccione M, Corsello G, Della Monica M, Scarano F, Priolo M, Gentile M, Zampino G, Vijzelaar R, et al.

J Med Genet. 2015 Dec;52(12):804-14. doi: 10.1136/jmedgenet-2015-103184. Epub 2015 Sep 30.

PubMed [citation]

PMID:: 26424144

Disease-associated mosaic variation in clinical exome sequencing: a two-year pediatric tertiary care experience.

Miller CR, Lee K, Pfau RB, Reshmi SC, Corsmeier DJ, Hashimoto S, Dave-Wala A, Jayaraman V, Koboldt D, Matthews T, Mouhlas D, Stein M, McKinney A, Grossman T, Kelly BJ, White P, Magrini V, Wilson RK, Mardis ER, Cottrell CE.

Cold Spring Harb Mol Case Stud. 2020 Jun 12;6(3). doi:pii: a005231. 10.1101/mcs.a005231. Print 2020 Jun.

PubMed [citation]

PMID:: 32371413
PMCID:: PMC7304353

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000742382.4

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

Description

The c.1042C>T (p.R348*) alteration, located in exon 2 (coding exon 1) of the KANSL1 gene, consists of a C to T substitution at nucleotide position 1042. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 348. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been detected in multiple individuals with Koolen-de Vries syndrome, including multiple cases of reported de novo occurrence (Zollino, 2015; Miller, 2020; St John, 2022). Based on the available evidence, this alteration is 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: Aug 11, 2024

ClinVar

Relating variation to medicine