ClinVar Genomic variation as it relates to human health
NM_013275.6(ANKRD11):c.7606C>T (p.Arg2536Trp)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_013275.6(ANKRD11):c.7606C>T (p.Arg2536Trp)
Variation ID: 1341546 Accession: VCV001341546.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q24.3 16: 89274921 (GRCh38) [ NCBI UCSC ] 16: 89341329 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 23, 2022 May 1, 2024 Jul 10, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_013275.6:c.7606C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_037407.4:p.Arg2536Trp missense NM_001256182.1:c.7606C>T NM_001256182.2:c.7606C>T NP_001243111.1:p.Arg2536Trp missense NM_001256183.2:c.7606C>T NP_001243112.1:p.Arg2536Trp missense NM_013275.4:c.7606C>T NM_013275.5:c.7606C>T NC_000016.10:g.89274921G>A NC_000016.9:g.89341329G>A NG_032003.2:g.220641C>T - Protein change
- R2536W
- Other names
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- Canonical SPDI
- NC_000016.10:89274920:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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ANKRD11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2514 | 2684 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jul 10, 2023 | RCV002275261.4 | |
Pathogenic (2) |
criteria provided, single submitter
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Nov 25, 2022 | RCV002222732.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 7, 2023 | RCV003163977.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Nov 01, 2021)
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criteria provided, single submitter
Method: research
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KBG syndrome
Affected status: yes
Allele origin:
de novo
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Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano
Accession: SCV002097358.1
First in ClinVar: Aug 23, 2022 Last updated: Aug 23, 2022 |
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Nov 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002499885.2
First in ClinVar: Apr 23, 2022 Last updated: Dec 11, 2022 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35682590, 35710456) (less)
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Likely pathogenic
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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KBG syndrome
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV003841558.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.42; 3Cnet: 0.73). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001341546). A different missense change at the same codon (p.Arg2536Gln) has been reported to be associated with ANKRD11-related disorder (ClinVar ID: VCV001012410). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less)
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Pathogenic
(Jul 10, 2023)
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criteria provided, single submitter
Method: clinical testing
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KBG syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004368498.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
Experimental studies have shown that this missense change affects ANKRD11 function (PMID: 35833929). For these reasons, this variant has been classified as Pathogenic. Advanced modeling … (more)
Experimental studies have shown that this missense change affects ANKRD11 function (PMID: 35833929). For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ANKRD11 protein function. ClinVar contains an entry for this variant (Variation ID: 1341546). This missense change has been observed in individual(s) with KBG syndrome (PMID: 35682590, 35833929). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 2536 of the ANKRD11 protein (p.Arg2536Trp). (less)
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Pathogenic
(Feb 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003892573.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The c.7606C>T (p.R2536W) alteration is located in exon 11 (coding exon 9) of the ANKRD11 gene. This alteration results from a C to T substitution … (more)
The c.7606C>T (p.R2536W) alteration is located in exon 11 (coding exon 9) of the ANKRD11 gene. This alteration results from a C to T substitution at nucleotide position 7606, causing the arginine (R) at amino acid position 2536 to be replaced by a tryptophan (W). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in multiple individuals with features of KBG syndrome (DECIPHER v.9.32; Bestetti, 2022; de Boer, 2022), and has been determined to be the result of a de novo mutation in two individuals (DECIPHER v.9.32; de Boer, 2022). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Functional studies suggest this alteration impacts protein stability; however, the physiological relevance of this finding is unclear (de Boer, 2022). This alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Accession: SCV002522496.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Missense variants in ANKRD11 cause KBG syndrome by impairment of stability or transcriptional activity of the encoded protein. | de Boer E | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 35833929 |
Reanalysis of exome negative patients with rare disease: a pragmatic workflow for diagnostic applications. | Schobers G | Genome medicine | 2022 | PMID: 35710456 |
Expanding the Molecular Spectrum of ANKRD11 Gene Defects in 33 Patients with a Clinical Presentation of KBG Syndrome. | Bestetti I | International journal of molecular sciences | 2022 | PMID: 35682590 |
DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources. | Firth HV | American journal of human genetics | 2009 | PMID: 19344873 |
Text-mined citations for rs2151701893 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.