10-27092420-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014915.3(ANKRD26):c.624A>G(p.Val208Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,607,082 control chromosomes in the GnomAD database, including 38,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4875 hom., cov: 32)

Exomes 𝑓: 0.20 ( 33778 hom. )

Consequence

ANKRD26
NM_014915.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.38

Publications

28 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 10-27092420-T-C is Benign according to our data. Variant chr10-27092420-T-C is described in ClinVar as Benign. ClinVar VariationId is 260473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.624A>G	p.Val208Val	synonymous_variant	Exon 4 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.624A>G	p.Val208Val	synonymous_variant	Exon 4 of 34	5	NM_014915.3	ENSP00000365255.4

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35778

AN:

151946

Hom.:

4853

Cov.:

show subpopulations

Gnomad AFR

AF:

0.310

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.223

GnomAD2 exomes

AF:

0.242

AC:

59829

AN:

247536

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.549

Gnomad FIN exome

AF:

0.253

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.195

AC:

284013

AN:

1455018

Hom.:

33778

Cov.:

AF XY:

0.199

AC XY:

144413

AN XY:

724138

show subpopulations

African (AFR)

AF:

0.305

AC:

10143

AN:

33308

American (AMR)

AF:

0.194

AC:

8628

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5605

AN:

26076

East Asian (EAS)

AF:

0.578

AC:

22881

AN:

39596

South Asian (SAS)

AF:

0.364

AC:

31298

AN:

86014

European-Finnish (FIN)

AF:

0.250

AC:

13244

AN:

52984

Middle Eastern (MID)

AF:

0.217

AC:

1168

AN:

5378

European-Non Finnish (NFE)

AF:

0.161

AC:

178014

AN:

1106996

Other (OTH)

AF:

0.217

AC:

13032

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

9727

19454

29182

38909

48636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6746

13492

20238

26984

33730

<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:

0.236

AC:

35847

AN:

152064

Hom.:

4875

Cov.:

AF XY:

0.245

AC XY:

18188

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.310

AC:

12866

AN:

41446

American (AMR)

AF:

0.197

AC:

3013

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

711

AN:

3472

East Asian (EAS)

AF:

0.554

AC:

2855

AN:

5154

South Asian (SAS)

AF:

0.385

AC:

1857

AN:

4824

European-Finnish (FIN)

AF:

0.257

AC:

2716

AN:

10570

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11125

AN:

67998

Other (OTH)

AF:

0.233

AC:

493

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1325

2650

3974

5299

6624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.187

Hom.:

9723

Bravo

AF:

0.232

Asia WGS

AF:

0.465

AC:

1615

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombocytopenia 2

Benign:3

Nov 22, 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. -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 08, 2018

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

- -

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.20

(source)

DANN

Benign

0.52

PhyloP100

-1.4

Mutation Taster

=100/0

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