NM_015443.4(KANSL1):c.836A>T (p.Asp279Val) AND Koolen-de Vries syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 19, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000701760.2

Allele description [Variation Report for NM_015443.4(KANSL1):c.836A>T (p.Asp279Val)]

NM_015443.4(KANSL1):c.836A>T (p.Asp279Val)

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.836A>T (p.Asp279Val)
HGVS:
  • NC_000017.11:g.46171308T>A
  • NG_032784.1:g.59067A>T
  • NM_001193465.2:c.836A>T
  • NM_001193466.2:c.836A>T
  • NM_001379198.1:c.836A>T
  • NM_015443.3:c.836A>T
  • NM_015443.4:c.836A>TMANE SELECT
  • NP_001180394.1:p.Asp279Val
  • NP_001180395.1:p.Asp279Val
  • NP_001366127.1:p.Asp279Val
  • NP_056258.1:p.Asp279Val
  • NP_056258.1:p.Asp279Val
  • NC_000017.10:g.44248674T>A
  • NM_001193466.1:c.836A>T
Protein change:
D279V
Links:
dbSNP: rs1567762446
NCBI 1000 Genomes Browser:
rs1567762446
Molecular consequence:
  • NM_001193465.2:c.836A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193466.2:c.836A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379198.1:c.836A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015443.3:c.836A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015443.4:c.836A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Koolen-de Vries syndrome (KDVS)
Synonyms:
17q21.31 microdeletion syndrome; 17q21.31 deletion syndrome; Monosomy 17q21.31; See all synonyms [MedGen]
Identifiers:
MedGen: C1864871; Orphanet: 96169; OMIM: 610443

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000830575Invitaecriteria provided, single submitter
Uncertain significance
(Apr 23, 2018)
germlineclinical testing

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

SCV001251584Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Feb 19, 2020)
unknownclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Koolen-de Vries Syndrome.

Koolen DA, Morgan A, de Vries BBA.

2010 Jan 26 [updated 2019 Jun 13]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.

PubMed [citation]
PMID:
20301783

Details of each submission

From Invitae, SCV000830575.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces aspartic acid with valine at codon 279 of the KANSL1 protein (p.Asp279Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with KANSL1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV001251584.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The KANSL1 3 c.836A>T (p.Asp279Val) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database in a region of good sequence coverage, so the variant is presumed to be rare. Based on the limited evidence, the p.Asp279Val variant variant is classified as a variant of unknown significance for Koolen-De Vries syndrome.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 4, 2021

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