rs12359281

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014915.3(ANKRD26):c.1273A>G(p.Ile425Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,605,428 control chromosomes in the GnomAD database, including 1,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 207 hom., cov: 32)

Exomes 𝑓: 0.026 ( 827 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.467

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

thrombocytopenia 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
acute myeloid leukemia
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
autosomal thrombocytopenia with normal platelets
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANKRD26 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012910664).

BP6

Variant 10-27064078-T-C is Benign according to our data. Variant chr10-27064078-T-C is described in ClinVar as Benign. ClinVar VariationId is 260457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.1273A>G	p.Ile425Val	missense_variant	Exon 12 of 34	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5 link	c.1273A>G	p.Ile425Val	missense_variant	Exon 12 of 34	5	NM_014915.3	ENSP00000365255.4

Frequencies

GnomAD3 genomes

AF:

0.0424

AC:

6443

AN:

151978

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0865

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0588

Gnomad FIN

AF:

0.0244

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0179

Gnomad OTH

AF:

0.0422

GnomAD2 exomes

AF:

0.0362

AC:

8955

AN:

247414

AF XY:

0.0362

show subpopulations

Gnomad AFR exome

AF:

0.0858

Gnomad AMR exome

AF:

0.0246

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0246

Gnomad NFE exome

AF:

0.0186

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0257

AC:

37363

AN:

1453332

Hom.:

827

Cov.:

AF XY:

0.0268

AC XY:

19373

AN XY:

723500

show subpopulations

African (AFR)

AF:

0.0835

AC:

2777

AN:

33250

American (AMR)

AF:

0.0238

AC:

1063

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

557

AN:

26092

East Asian (EAS)

AF:

0.100

AC:

3969

AN:

39596

South Asian (SAS)

AF:

0.0592

AC:

5087

AN:

85896

European-Finnish (FIN)

AF:

0.0291

AC:

1485

AN:

51104

Middle Eastern (MID)

AF:

0.0466

AC:

267

AN:

5728

European-Non Finnish (NFE)

AF:

0.0183

AC:

20245

AN:

1106816

Other (OTH)

AF:

0.0318

AC:

1913

AN:

60162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1569

3138

4708

6277

7846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0424

AC:

6448

AN:

152096

Hom.:

207

Cov.:

AF XY:

0.0421

AC XY:

3127

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0864

AC:

3584

AN:

41460

American (AMR)

AF:

0.0171

AC:

262

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

3468

East Asian (EAS)

AF:

0.114

AC:

591

AN:

5164

South Asian (SAS)

AF:

0.0584

AC:

282

AN:

4826

European-Finnish (FIN)

AF:

0.0244

AC:

258

AN:

10572

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0179

AC:

1217

AN:

68018

Other (OTH)

AF:

0.0423

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

301

602

904

1205

1506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0265

Hom.:

266

Bravo

AF:

0.0438

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.0891

AC:

318

ESP6500EA

AF:

0.0202

AC:

164

ExAC

AF:

0.0374

AC:

4510

Asia WGS

AF:

0.0660

AC:

230

AN:

3466

EpiCase

AF:

0.0182

EpiControl

AF:

0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombocytopenia 2

Benign:3

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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 28, 2019

GeneDx

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

.;L

PhyloP100

-0.47

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.062

Sift

Benign

0.35

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0010

.;B

Vest4

0.018

MPC

0.045

ClinPred

0.00045

GERP RS

-2.8

Varity_R

0.045

gMVP

0.0073

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over