NM_015443.4(KANSL1):c.454G>A (p.Ala152Thr) AND Koolen-de Vries syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 17, 2021
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:: RCV001863951.4

Allele description [Variation Report for NM_015443.4(KANSL1):c.454G>A (p.Ala152Thr)]

NM_015443.4(KANSL1):c.454G>A (p.Ala152Thr)

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.454G>A (p.Ala152Thr)

HGVS:

NC_000017.11:g.46171690C>T
NG_032784.1:g.58685G>A
NM_001193465.2:c.454G>A
NM_001193466.2:c.454G>A
NM_001379198.1:c.454G>A
NM_015443.4:c.454G>AMANE SELECT
NP_001180394.1:p.Ala152Thr
NP_001180395.1:p.Ala152Thr
NP_001366127.1:p.Ala152Thr
NP_056258.1:p.Ala152Thr
NC_000017.10:g.44249056C>T

Protein change:

A152T

Links:

dbSNP: rs538005482

NCBI 1000 Genomes Browser:

rs538005482

Molecular consequence:

NM_001193465.2:c.454G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001193466.2:c.454G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379198.1:c.454G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015443.4:c.454G>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

Recent activity

Clear Turn Off Turn On

PRJNA261990 (179)
SRA
XYN2_EMENI Endo-1,4-beta-xylanase 2 precursor (Xylanase 2) (1,4-beta-D-xylan xyl...
XYN2_EMENI Endo-1,4-beta-xylanase 2 precursor (Xylanase 2) (1,4-beta-D-xylan xylanohydrolase 2) [Aspergillus nidulans FGSC A4]
gi|40747276|gb|EAA66432.1||gnl|WGS: AN9365.2

Protein
30S ribosomal protein S12 [Orientia tsutsugamushi str. Ikeda]
30S ribosomal protein S12 [Orientia tsutsugamushi str. Ikeda]
gi|189180862|dbj|BAG40642.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002127259	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 17, 2021)	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

SCV002127259

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 17, 2021)

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 Invitae, SCV002127259.2

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

Description

Due to the possible presence of a polymorphic segmental duplication, the location of the variant could not be unambiguously resolved. Variants with ambiguous mapping are still reported relative to the KANSL1 transcript. This sequence change replaces alanine with threonine at codon 152 of the KANSL1 protein (p.Ala152Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

#	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: Dec 24, 2023

ClinVar

Relating variation to medicine