NM_015443.4(KANSL1):c.2260G>A (p.Val754Met) AND Koolen-de Vries syndrome

Clinical significance:Uncertain significance (Last evaluated: Aug 22, 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:: RCV001339007.5

Allele description [Variation Report for NM_015443.4(KANSL1):c.2260G>A (p.Val754Met)]

NM_015443.4(KANSL1):c.2260G>A (p.Val754Met)

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.2260G>A (p.Val754Met)

HGVS:

NC_000017.11:g.46039159C>T
NG_032784.1:g.191216G>A
NM_001193465.2:c.2260G>A
NM_001193466.2:c.2260G>A
NM_001379198.1:c.2260G>A
NM_015443.4:c.2260G>AMANE SELECT
NP_001180394.1:p.Val754Met
NP_001180395.1:p.Val754Met
NP_001366127.1:p.Val754Met
NP_056258.1:p.Val754Met
NC_000017.10:g.44116525C>T

Protein change:

V754M

Links:

dbSNP: rs773184800

NCBI 1000 Genomes Browser:

rs773184800

Molecular consequence:

NM_001193465.2:c.2260G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001193466.2:c.2260G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379198.1:c.2260G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015443.4:c.2260G>A - 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
SCV001532720	Invitae	criteria provided, single submitter Invitae Variant Classification Sherloc (09022015)	Uncertain significance (Aug 22, 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

SCV001532720

Invitae

criteria provided, single submitter

Invitae Variant Classification Sherloc (09022015)

Uncertain significance
(Aug 22, 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, SCV001532720.3

#	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 valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 754 of the KANSL1 protein (p.Val754Met). This variant is present in population databases (rs773184800, gnomAD 0.007%). 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: 1036055). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 7, 2023

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