NM_015443.4(KANSL1):c.992A>G (p.Lys331Arg) AND Koolen-de Vries syndrome

Clinical significance:Uncertain significance (Last evaluated: Sep 9, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001223492.2

Allele description [Variation Report for NM_015443.4(KANSL1):c.992A>G (p.Lys331Arg)]

NM_015443.4(KANSL1):c.992A>G (p.Lys331Arg)

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.992A>G (p.Lys331Arg)
HGVS:
  • NC_000017.11:g.46171152T>C
  • NG_032784.1:g.59223A>G
  • NM_001193465.2:c.992A>G
  • NM_001193466.2:c.992A>G
  • NM_001379198.1:c.992A>G
  • NM_015443.4:c.992A>GMANE SELECT
  • NP_001180394.1:p.Lys331Arg
  • NP_001180395.1:p.Lys331Arg
  • NP_001366127.1:p.Lys331Arg
  • NP_056258.1:p.Lys331Arg
  • NC_000017.10:g.44248518T>C
  • NM_001193466.1:c.992A>G
Protein change:
K331R
Links:
dbSNP: rs570475423
NCBI 1000 Genomes Browser:
rs570475423
Molecular consequence:
  • NM_001193465.2:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193466.2:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379198.1:c.992A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015443.4:c.992A>G - 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
SCV001395644Invitaecriteria provided, single submitter
Uncertain significance
(Sep 9, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
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

Details of each submission

From Invitae, SCV001395644.2

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

Description

Due to the possible presence of a polymorphic segmental duplication, the location of the variant could not be unambiguously resolved. If the variant occurs in the KANSL1 gene, this sequence change replaces lysine with arginine at codon 331 of the KANSL1 protein (p.Lys331Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has not been reported in the literature in individuals with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 951545). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C2. The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Until the location of this sequence change can be resolved, the clinical significance of this variant remains uncertain. It has been classified as a Variant of Uncertain Significance. 5

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

Last Updated: Nov 27, 2021

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