NM_014915.3:c.59A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014915.3(ANKRD26):c.59A>G(p.Gln20Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,610,676 control chromosomes in the GnomAD database, including 612,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62363 hom., cov: 34)

Exomes 𝑓: 0.87 ( 549740 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.09

Variant links:

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]

ANKRD26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.475063E-7).

BP6

Variant 10-27100268-T-C is Benign according to our data. Variant chr10-27100268-T-C is described in ClinVar as [Benign]. Clinvar id is 260472.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27100268-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.59A>G	p.Gln20Arg	missense_variant	Exon 1 of 34	ENST00000376087.5	NP_055730.2	Q9UPS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5 link	c.59A>G	p.Gln20Arg	missense_variant	Exon 1 of 34	5	NM_014915.3	ENSP00000365255.4		Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.903

AC:

137435

AN:

152202

Hom.:

62298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.972

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.902

Gnomad ASJ

AF:

0.872

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.923

Gnomad FIN

AF:

0.931

Gnomad MID

AF:

0.851

Gnomad NFE

AF:

0.851

Gnomad OTH

AF:

0.887

GnomAD3 exomes

AF:

0.899

AC:

218953

AN:

243526

Hom.:

98716

AF XY:

0.896

AC XY:

119116

AN XY:

132984

show subpopulations

Gnomad AFR exome

AF:

0.974

Gnomad AMR exome

AF:

0.933

Gnomad ASJ exome

AF:

0.877

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.921

Gnomad FIN exome

AF:

0.930

Gnomad NFE exome

AF:

0.853

Gnomad OTH exome

AF:

0.882

GnomAD4 exome

AF:

0.867

AC:

1264775

AN:

1458356

Hom.:

549740

Cov.:

AF XY:

0.868

AC XY:

629994

AN XY:

725536

show subpopulations

Gnomad4 AFR exome

AF:

0.975

Gnomad4 AMR exome

AF:

0.929

Gnomad4 ASJ exome

AF:

0.875

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.918

Gnomad4 FIN exome

AF:

0.925

Gnomad4 NFE exome

AF:

0.849

Gnomad4 OTH exome

AF:

0.879

GnomAD4 genome

AF:

0.903

AC:

137559

AN:

152320

Hom.:

62363

Cov.:

AF XY:

0.909

AC XY:

67724

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.972

Gnomad4 AMR

AF:

0.902

Gnomad4 ASJ

AF:

0.872

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.923

Gnomad4 FIN

AF:

0.931

Gnomad4 NFE

AF:

0.851

Gnomad4 OTH

AF:

0.888

Alfa

AF:

0.861

Hom.:

34184

Bravo

AF:

0.904

TwinsUK

AF:

0.849

AC:

3149

ALSPAC

AF:

0.855

AC:

3297

ESP6500AA

AF:

0.973

AC:

3584

ESP6500EA

AF:

0.857

AC:

6982

ExAC

AF:

0.896

AC:

107448

Asia WGS

AF:

0.967

AC:

3362

AN:

3478

EpiCase

AF:

0.855

EpiControl

AF:

0.855

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Thrombocytopenia 2

Benign:3

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21467542) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.076

DANN

Benign

0.66

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

8.5e-7

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

.;N

PrimateAI

Benign

0.32

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.0050

Sift

Benign

1.0

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.0

.;B

Vest4

0.043

MPC

0.049

ClinPred

0.0022

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over