rs10829163

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.3913G>A(p.Val1305Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,610,364 control chromosomes in the GnomAD database, including 31,558 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3634 hom., cov: 32)

Exomes 𝑓: 0.17 ( 27924 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.89

Publications

34 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
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

new If you want to explore the variant's impact on the transcript NM_014915.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=3.16597E-5).

BP6

Variant 10-27028911-C-T is Benign according to our data. Variant chr10-27028911-C-T is described in ClinVar as Benign. ClinVar VariationId is 260467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014915.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD26	NM_014915.3	MANE Select	c.3913G>A	p.Val1305Ile	missense	Exon 27 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.3910G>A	p.Val1304Ile	missense	Exon 27 of 34	NP_001242982.1	E7ESJ3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD26	ENST00000376087.5	TSL:5 MANE Select	c.3913G>A	p.Val1305Ile	missense	Exon 27 of 34	ENSP00000365255.4	Q9UPS8-1
ANKRD26	ENST00000436985.7	TSL:1	c.3910G>A	p.Val1304Ile	missense	Exon 27 of 34	ENSP00000405112.3	E7ESJ3
ANKRD26	ENST00000968143.1		c.4999G>A	p.Val1667Ile	missense	Exon 28 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30319

AN:

151882

Hom.:

3616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.194

GnomAD2 exomes

AF:

0.220

AC:

54765

AN:

248564

AF XY:

0.224

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.550

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.172

AC:

251471

AN:

1458364

Hom.:

27924

Cov.:

AF XY:

0.177

AC XY:

128525

AN XY:

725572

show subpopulations

African (AFR)

AF:

0.222

AC:

7416

AN:

33422

American (AMR)

AF:

0.181

AC:

8100

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

5050

AN:

26084

East Asian (EAS)

AF:

0.577

AC:

22798

AN:

39518

South Asian (SAS)

AF:

0.343

AC:

29414

AN:

85810

European-Finnish (FIN)

AF:

0.236

AC:

12560

AN:

53328

Middle Eastern (MID)

AF:

0.190

AC:

1093

AN:

5756

European-Non Finnish (NFE)

AF:

0.138

AC:

153308

AN:

1109556

Other (OTH)

AF:

0.195

AC:

11732

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

9854

19707

29561

39414

49268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5902

11804

17706

23608

29510

<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:

0.200

AC:

30386

AN:

152000

Hom.:

3634

Cov.:

AF XY:

0.210

AC XY:

15598

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.226

AC:

9348

AN:

41450

American (AMR)

AF:

0.179

AC:

2731

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.187

AC:

649

AN:

3470

East Asian (EAS)

AF:

0.558

AC:

2880

AN:

5160

South Asian (SAS)

AF:

0.368

AC:

1776

AN:

4822

European-Finnish (FIN)

AF:

0.244

AC:

2575

AN:

10536

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.144

AC:

9797

AN:

67964

Other (OTH)

AF:

0.204

AC:

431

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1166

2331

3497

4662

5828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.166

Hom.:

8649

Bravo

AF:

0.193

Asia WGS

AF:

0.456

AC:

1577

AN:

3464

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Thrombocytopenia 2 (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.14

(source)

DANN

Benign

0.11

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.11

MetaRNN

Benign

0.000032

MetaSVM

Benign

-1.0

PhyloP100

-1.9

PrimateAI

Benign

0.34

PROVEAN

Benign

0.040

REVEL

Benign

0.070

Sift

Benign

1.0

Sift4G

Benign

1.0

Varity_R

0.014

gMVP

0.011

Mutation Taster

=99/1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over