NM_015443.4(KANSL1):c.2940G>C (p.Leu980Phe) AND Koolen-de Vries syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 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:: RCV002304502.4

Allele description [Variation Report for NM_015443.4(KANSL1):c.2940G>C (p.Leu980Phe)]

NM_015443.4(KANSL1):c.2940G>C (p.Leu980Phe)

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.2940G>C (p.Leu980Phe)

HGVS:

NC_000017.11:g.46032197C>G
NG_032784.1:g.198178G>C
NM_001193465.2:c.2937G>C
NM_001193466.2:c.2940G>C
NM_001379198.1:c.2940G>C
NM_001405854.1:c.2940G>C
NM_001405855.1:c.2940G>C
NM_001405856.1:c.2937G>C
NM_001405857.1:c.2937G>C
NM_001405858.1:c.2937G>C
NM_001405859.1:c.2838G>C
NM_001405860.1:c.2838G>C
NM_001405861.1:c.2835G>C
NM_001405875.1:c.2751G>C
NM_001405876.1:c.2751G>C
NM_001405877.1:c.2751G>C
NM_001405878.1:c.2751G>C
NM_001405879.1:c.2748G>C
NM_001405880.1:c.2748G>C
NM_001405882.1:c.1674G>C
NM_001405883.1:c.1671G>C
NM_001405884.1:c.1485G>C
NM_001405885.1:c.1482G>C
NM_015443.4:c.2940G>CMANE SELECT
NP_001180394.1:p.Leu979Phe
NP_001180395.1:p.Leu980Phe
NP_001366127.1:p.Leu980Phe
NP_001392783.1:p.Leu980Phe
NP_001392784.1:p.Leu980Phe
NP_001392785.1:p.Leu979Phe
NP_001392786.1:p.Leu979Phe
NP_001392787.1:p.Leu979Phe
NP_001392788.1:p.Leu946Phe
NP_001392789.1:p.Leu946Phe
NP_001392790.1:p.Leu945Phe
NP_001392804.1:p.Leu917Phe
NP_001392805.1:p.Leu917Phe
NP_001392806.1:p.Leu917Phe
NP_001392807.1:p.Leu917Phe
NP_001392808.1:p.Leu916Phe
NP_001392809.1:p.Leu916Phe
NP_001392811.1:p.Leu558Phe
NP_001392812.1:p.Leu557Phe
NP_001392813.1:p.Leu495Phe
NP_001392814.1:p.Leu494Phe
NP_056258.1:p.Leu980Phe
NC_000017.10:g.44109563C>G

Protein change:

L494F

Molecular consequence:

NM_001193465.2:c.2937G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001193466.2:c.2940G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001379198.1:c.2940G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405854.1:c.2940G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405855.1:c.2940G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405856.1:c.2937G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405857.1:c.2937G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405858.1:c.2937G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405859.1:c.2838G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405860.1:c.2838G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405861.1:c.2835G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405875.1:c.2751G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405876.1:c.2751G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405877.1:c.2751G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405878.1:c.2751G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405879.1:c.2748G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405880.1:c.2748G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405882.1:c.1674G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405883.1:c.1671G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405884.1:c.1485G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001405885.1:c.1482G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015443.4:c.2940G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002591998	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2024)	germline	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

SCV002591998

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2024)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002591998.3

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 980 of the KANSL1 protein (p.Leu980Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1715217). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KANSL1 protein function with a negative predictive value of 80%. 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.

#	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: Sep 29, 2024

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Relating variation to medicine