NM_015443.4(KANSL1):c.631C>G (p.Pro211Ala) AND Koolen-de Vries syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 5, 2022
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:: RCV001206043.5

Allele description [Variation Report for NM_015443.4(KANSL1):c.631C>G (p.Pro211Ala)]

NM_015443.4(KANSL1):c.631C>G (p.Pro211Ala)

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.631C>G (p.Pro211Ala)

HGVS:

NC_000017.11:g.46171513G>C
NG_032784.1:g.58862C>G
NM_001193465.2:c.631C>G
NM_001193466.2:c.631C>G
NM_001379198.1:c.631C>G
NM_015443.4:c.631C>GMANE SELECT
NP_001180394.1:p.Pro211Ala
NP_001180395.1:p.Pro211Ala
NP_001366127.1:p.Pro211Ala
NP_056258.1:p.Pro211Ala
NC_000017.10:g.44248879G>C
NM_001193466.1:c.631C>G

Protein change:

P211A

Links:

dbSNP: rs745305837

NCBI 1000 Genomes Browser:

rs745305837

Molecular consequence:

NM_001193465.2:c.631C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001193466.2:c.631C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001379198.1:c.631C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015443.4:c.631C>G - 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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Syzygium maire plastid external transcribed spacer, ETS, specimen voucher Belsha...
Syzygium maire plastid external transcribed spacer, ETS, specimen voucher Belsham M84 (OTA)
gi|164509004|emb|AM489968.1|

Nucleotide
negr1 neuronal growth regulator 1 [Danio rerio]
negr1 neuronal growth regulator 1 [Danio rerio]
Gene ID:445374

Gene
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Profile neighbors for GEO Profiles (Select 71254912) (199)
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Chromosome neighbors for GEO Profiles (Select 71242691) (20)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001377330	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002779366	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 5, 2022)	unknown	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

SCV001377330

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 2, 2021)

germline

clinical testing

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

SCV002779366

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 5, 2022)

unknown

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
not provided	unknown	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

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, SCV001377330.3

#	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 proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 211 of the KANSL1 or 17q21.31 segmental duplication protein (p.Pro211Ala). The frequency data for this variant in the population databases (gnomAD) 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. ClinVar contains an entry for this variant (Variation ID: 937095). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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

From Fulgent Genetics, Fulgent Genetics, SCV002779366.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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