NM_015443.4(KANSL1):c.1937C>T (p.Pro646Leu) AND Koolen-de Vries syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 27, 2022)
Review status:1 star out of maximum of 4 stars
criteria provided, single submitter

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Based on:: 1 submission [Details]
Record status:: current
Accession:: RCV001346147.4

Allele description [Variation Report for NM_015443.4(KANSL1):c.1937C>T (p.Pro646Leu)]

NM_015443.4(KANSL1):c.1937C>T (p.Pro646Leu)

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.1937C>T (p.Pro646Leu)

Other names:

p.P646L:CCC>CTC

HGVS:

NC_000017.11:g.46050616G>A
NG_032784.1:g.179759C>T
NM_001193465.2:c.1937C>T
NM_001193466.2:c.1937C>T
NM_001379198.1:c.1937C>T
NM_015443.4:c.1937C>TMANE SELECT
NP_001180394.1:p.Pro646Leu
NP_001180395.1:p.Pro646Leu
NP_001366127.1:p.Pro646Leu
NP_056258.1:p.Pro646Leu
NC_000017.10:g.44127982G>A
NM_001193466.1:c.1937C>T

Protein change:

P646L

Links:

dbSNP: rs796052585

NCBI 1000 Genomes Browser:

rs796052585

Molecular consequence:

NM_001193465.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001193466.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379198.1:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015443.4:c.1937C>T - 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
SCV001540323	Invitae	criteria provided, single submitter Invitae Variant Classification Sherloc (09022015)	Uncertain significance (Oct 27, 2022)	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

SCV001540323

Invitae

criteria provided, single submitter

Invitae Variant Classification Sherloc (09022015)

Uncertain significance
(Oct 27, 2022)

germline

clinical testing

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

Summary from all submissions

Help

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001540323.3

#	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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 646 of the KANSL1 protein (p.Pro646Leu). 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: 205738). 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. 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: Feb 18, 2023

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