rs12572862

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.3658G>C(p.Val1220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,608,624 control chromosomes in the GnomAD database, including 1,801 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 0.016 ( 156 hom., cov: 32)

Exomes 𝑓: 0.017 ( 1645 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.416

Publications

9 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=0.0017209053).

BP6

Variant 10-27033374-C-G is Benign according to our data. Variant chr10-27033374-C-G is described in ClinVar as Benign. ClinVar VariationId is 260466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.3658G>C	p.Val1220Leu	missense_variant	Exon 25 of 34	ENST00000376087.5	NP_055730.2	Q9UPS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANKRD26	ENST00000376087.5 link	c.3658G>C	p.Val1220Leu	missense_variant	Exon 25 of 34	5	NM_014915.3	ENSP00000365255.4	Q9UPS8-1
ANKRD26	ENST00000436985.7 link	c.3655G>C	p.Val1219Leu	missense_variant	Exon 25 of 34	1		ENSP00000405112.3	E7ESJ3
ANKRD26	ENST00000675116.1 link	n.1306G>C		non_coding_transcript_exon_variant	Exon 5 of 15			ENSP00000501975.1	A0A6Q8PFU2
ANKRD26	ENST00000675936.1 link	n.73G>C		non_coding_transcript_exon_variant	Exon 2 of 13			ENSP00000502093.1	A0A6Q8PG48

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2509

AN:

152080

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0144

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0547

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.00814

GnomAD2 exomes

AF:

0.0357

AC:

8895

AN:

249158

AF XY:

0.0388

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.00963

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.0569

Gnomad NFE exome

AF:

0.00350

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0169

AC:

24559

AN:

1456426

Hom.:

1645

Cov.:

AF XY:

0.0196

AC XY:

14192

AN XY:

724464

show subpopulations

African (AFR)

AF:

0.000718

AC:

AN:

33434

American (AMR)

AF:

0.0274

AC:

1223

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.0100

AC:

261

AN:

26014

East Asian (EAS)

AF:

0.203

AC:

8032

AN:

39470

South Asian (SAS)

AF:

0.111

AC:

9483

AN:

85188

European-Finnish (FIN)

AF:

0.0530

AC:

2813

AN:

53066

Middle Eastern (MID)

AF:

0.00873

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00140

AC:

1554

AN:

1108786

Other (OTH)

AF:

0.0186

AC:

1119

AN:

60066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

948

1896

2844

3792

4740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.0165

AC:

2505

AN:

152198

Hom.:

156

Cov.:

AF XY:

0.0220

AC XY:

1636

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41552

American (AMR)

AF:

0.0143

AC:

219

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3470

East Asian (EAS)

AF:

0.158

AC:

816

AN:

5176

South Asian (SAS)

AF:

0.128

AC:

616

AN:

4826

European-Finnish (FIN)

AF:

0.0547

AC:

578

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00266

AC:

181

AN:

67992

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

103

207

310

414

517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.00594

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.00220

AC:

ExAC

AF:

0.0359

AC:

4339

Asia WGS

AF:

0.117

AC:

406

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombocytopenia 2

Benign:3

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. -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 02, 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

- -

Mar 02, 2019

GeneDx

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

0.32

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.9

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.074

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.074

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.99

PhyloP100

0.42

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.096

Sift

Benign

0.070

T;T

Sift4G

Benign

0.27

T;T

Vest4

0.033

MPC

0.055

ClinPred

0.0066

GERP RS

-3.7

Varity_R

0.054

gMVP

0.031

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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