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NM_015443.4(KANSL1):c.442G>A (p.Ala148Thr) AND Koolen-de Vries syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Oct 13, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001048513.9

Allele description [Variation Report for NM_015443.4(KANSL1):c.442G>A (p.Ala148Thr)]

NM_015443.4(KANSL1):c.442G>A (p.Ala148Thr)

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.442G>A (p.Ala148Thr)
HGVS:
  • NC_000017.11:g.46171702C>T
  • NG_032784.1:g.58673G>A
  • NM_001193465.2:c.442G>A
  • NM_001193466.2:c.442G>A
  • NM_001379198.1:c.442G>A
  • NM_015443.4:c.442G>AMANE SELECT
  • NP_001180394.1:p.Ala148Thr
  • NP_001180395.1:p.Ala148Thr
  • NP_001366127.1:p.Ala148Thr
  • NP_056258.1:p.Ala148Thr
  • NC_000017.10:g.44249068C>T
  • NM_001193466.1:c.442G>A
Protein change:
A148T
Links:
dbSNP: rs140089320
NCBI 1000 Genomes Browser:
rs140089320
Molecular consequence:
  • NM_001193465.2:c.442G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193466.2:c.442G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379198.1:c.442G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015443.4:c.442G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001212524Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 10, 2020) 		germlineclinical testing

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

SCV002792772Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 13, 2021) 		unknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical 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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001212524.5

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KANSL1-related conditions. This variant is present in population databases (rs140089320, ExAC 0.03%). This sequence change replaces alanine with threonine at codon 148 of the KANSL1 protein (p.Ala148Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.

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

From Fulgent Genetics, Fulgent Genetics, SCV002792772.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024