rs75445709

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_014915.3(ANKRD26):c.2376-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,605,426 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 117 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 108 hom. )

Consequence

ANKRD26
NM_014915.3 splice_region, intron

Scores

Splicing: ADA: 0.001268

Clinical Significance

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

Conservation

PhyloP100: 0.566

Publications

1 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 10-27038058-C-T is Benign according to our data. Variant chr10-27038058-C-T is described in ClinVar as [Benign]. Clinvar id is 260462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.2376-4G>A		splice_region_variant, intron_variant	Intron 21 of 33	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.2376-4G>A		splice_region_variant, intron_variant	Intron 21 of 33	5	NM_014915.3	ENSP00000365255.4		Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3172

AN:

152044

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00707

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00537

AC:

1314

AN:

244792

AF XY:

0.00417

show subpopulations

Gnomad AFR exome

AF:

0.0761

Gnomad AMR exome

AF:

0.00268

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.000447

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00216

AC:

3140

AN:

1453264

Hom.:

108

Cov.:

AF XY:

0.00188

AC XY:

1361

AN XY:

723296

show subpopulations

African (AFR)

AF:

0.0778

AC:

2589

AN:

33280

American (AMR)

AF:

0.00314

AC:

140

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.000152

AC:

AN:

39516

South Asian (SAS)

AF:

0.000221

AC:

AN:

86020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48708

Middle Eastern (MID)

AF:

0.00369

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000721

AC:

AN:

1109110

Other (OTH)

AF:

0.00473

AC:

285

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

129

258

388

517

646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0209

AC:

3174

AN:

152162

Hom.:

117

Cov.:

AF XY:

0.0200

AC XY:

1485

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0727

AC:

3017

AN:

41488

American (AMR)

AF:

0.00706

AC:

108

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5172

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68014

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

151

302

452

603

754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00751

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.00145

AC:

AN:

3470

EpiCase

AF:

0.000109

EpiControl

AF:

0.000298

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombocytopenia 2

Benign:3

Oct 17, 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

- -

Jan 08, 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

- -

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

-0.41

CADD

Benign

8.8

(source)

DANN

Benign

0.58

PhyloP100

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.046

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.

rs75445709

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