NM_015443.4(KANSL1):c.1042C>T (p.Arg348Ter) AND Koolen-de Vries syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Aug 30, 2021
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:: RCV000852304.8

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:: Koolen-de Vries syndrome (KDVS)
Synonyms:: KANSL1-Related Intellectual Disability Syndrome
Identifiers:: MONDO: MONDO:0012496; MedGen: C1864871; Orphanet: 96169; OMIM: 610443

Recent activity

Clear Turn Off Turn On

Homo sapiens myelin oligodendrocyte glycoprotein (MOG), RefSeqGene on chromosome...
Homo sapiens myelin oligodendrocyte glycoprotein (MOG), RefSeqGene on chromosome 6
gi|359718920|ref|NG_031873.1|

Nucleotide
plastin-1 isoform X1 [Homo sapiens]
plastin-1 isoform X1 [Homo sapiens]
gi|2217344401|ref|XP_047304278.1|

Protein
3-4 toe cutaneous syndactyly
3-4 toe cutaneous syndactyly

MedGen
4-5 toe cutaneous syndactyly
4-5 toe cutaneous syndactyly

MedGen
1-2 toe complete cutaneous syndactyly
1-2 toe complete cutaneous syndactyly

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
SCV000994929	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 5, 2019)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 26424144, 25741868
SCV001423660	Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 31, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001950120	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 30, 2021)	paternal	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

SCV000994929

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 5, 2019)

unknown

curation

PubMed (2)
[See all records that cite these PMIDs]

SCV001423660

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 31, 2018)

germline

clinical testing

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

SCV001950120

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 30, 2021)

paternal

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
not provided	paternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

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

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 SIB Swiss Institute of Bioinformatics, SCV000994929.1

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

Description

This variant is interpreted as a Pathogenic for Koolen-De Vries syndrome, autosomal dominant. The following ACMG Tag(s) were applied: PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6: Assumed de novo, but without confirmation of paternity and maternity. PVS1: Predicted nullvariant in a gene where LOF is a known mechanism of disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital, SCV001423660.1

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

Description

[ACMG/AMP: PVS1, PS2, PM2, PP5] This alteration is a null variant in a gene where LOF is a known mechanism of disease [PVS1], is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is absent from or rarely observed in large-scale population databases [PM2], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5].

#	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 Institute of Human Genetics, University of Leipzig Medical Center, SCV001950120.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 11, 2024

ClinVar

Relating variation to medicine