rs139949439
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014915.3(ANKRD26):āc.2332G>Cā(p.Glu778Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00321 in 1,613,662 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0024 ( 2 hom., cov: 32)
Exomes š: 0.0033 ( 9 hom. )
Consequence
ANKRD26
NM_014915.3 missense
NM_014915.3 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 3.96
Genes affected
ANKRD26 (HGNC:29186): (ankyrin repeat domain containing 26) This gene encodes a protein containing N-terminal ankyrin repeats which function in protein-protein interactions. Mutations in this gene are associated with autosomal dominant thrombocytopenia-2. Pseudogenes of this gene are found on chromosome 7, 10, 13 and 16. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009538174).
BP6
?
Variant 10-27040008-C-G is Benign according to our data. Variant chr10-27040008-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 434202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0024 (365/152322) while in subpopulation NFE AF= 0.00397 (270/68022). AF 95% confidence interval is 0.00358. There are 2 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 365 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANKRD26 | NM_014915.3 | c.2332G>C | p.Glu778Gln | missense_variant | 21/34 | ENST00000376087.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANKRD26 | ENST00000376087.5 | c.2332G>C | p.Glu778Gln | missense_variant | 21/34 | 5 | NM_014915.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00240 AC: 365AN: 152204Hom.: 2 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00221 AC: 552AN: 249402Hom.: 1 AF XY: 0.00225 AC XY: 304AN XY: 135330
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GnomAD4 exome AF: 0.00329 AC: 4810AN: 1461340Hom.: 9 Cov.: 31 AF XY: 0.00325 AC XY: 2365AN XY: 727010
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GnomAD4 genome ? AF: 0.00240 AC: 365AN: 152322Hom.: 2 Cov.: 32 AF XY: 0.00230 AC XY: 171AN XY: 74484
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ESP6500AA
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 05, 2021 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | ANKRD26: BP4, BS1, BS2 - |
Thrombocytopenia 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 30, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Vest4
MVP
MPC
0.32
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at