NM_015443.4(KANSL1):c.808_809del (p.Leu270fs) AND Koolen-de Vries syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Jul 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000551044.5

Allele description [Variation Report for NM_015443.4(KANSL1):c.808_809del (p.Leu270fs)]

NM_015443.4(KANSL1):c.808_809del (p.Leu270fs)

Gene:
KANSL1:KAT8 regulatory NSL complex subunit 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_015443.4(KANSL1):c.808_809del (p.Leu270fs)
HGVS:
  • NC_000017.11:g.46171335_46171336del
  • NG_032784.1:g.59039_59040del
  • NM_001193465.2:c.808_809del
  • NM_001193466.2:c.808_809del
  • NM_001379198.1:c.808_809del
  • NM_015443.4:c.808_809delMANE SELECT
  • NP_001180394.1:p.Leu270fs
  • NP_001180395.1:p.Leu270fs
  • NP_001366127.1:p.Leu270fs
  • NP_056258.1:p.Leu270fs
  • NC_000017.10:g.44248701_44248702del
  • NC_000017.10:g.44248701_44248702del
  • NM_001193466.1:c.808_809del
  • NM_001193466.1:c.808_809delCT
Protein change:
L270fs
Links:
dbSNP: rs551541795
NCBI 1000 Genomes Browser:
rs551541795
Molecular consequence:
  • NM_001193465.2:c.808_809del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001193466.2:c.808_809del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001379198.1:c.808_809del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_015443.4:c.808_809del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000645070Invitaecriteria provided, single submitter
Uncertain significance
(Jul 8, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001529643Baylor Geneticscriteria provided, single submitter
Pathogenic
(Sep 28, 2018)
de novoclinical 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
not providedde novoyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Contribution of next generation sequencing in pediatric practice in Lebanon. A Study on 213 cases.

Nair P, Sabbagh S, Mansour H, Fawaz A, Hmaimess G, Noun P, Dagher R, Megarbane H, Hana S, Alame S, Lamaa M, Hasbini D, Farah R, Rajab M, Stora S, El-Tourjuman O, Abou Jaoude P, Chalouhi G, Sayad R, Gillart AC, Al-Ali M, Delague V, et al.

Mol Genet Genomic Med. 2018 Nov;6(6):1041-1052. doi: 10.1002/mgg3.480. Epub 2018 Oct 7.

PubMed [citation]
PMID:
30293248
PMCID:
PMC6305638

Clinically-relevant postzygotic mosaicism in parents and children with developmental disorders in trio exome sequencing data.

Wright CF, Prigmore E, Rajan D, Handsaker J, McRae J, Kaplanis J, Fitzgerald TW, FitzPatrick DR, Firth HV, Hurles ME.

Nat Commun. 2019 Jul 5;10(1):2985. doi: 10.1038/s41467-019-11059-2.

PubMed [citation]
PMID:
31278258
PMCID:
PMC6611863
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000645070.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

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 creates a premature translational stop signal (p.Leu270Valfs*11) in the KANSL1 gene. It is expected to result in an absent or disrupted protein product. 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 been observed in individual(s) with neurological and developmental disorders (PMID: 30293248, 31278258). ClinVar contains an entry for this variant (Variation ID: 468412). Loss-of-function variants in KANSL1 are known to be pathogenic (PMID: 22544363, 22544367). If this variant occurs in KANSL1, it is expected to be pathogenic. However, due to the uncertainty of the location of this sequence change, it has been classified as a Variant of Uncertain Significance.

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

From Baylor Genetics, SCV001529643.1

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

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

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