10-27035066-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_014915.3(ANKRD26):c.3384G>A(p.Lys1128Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,613,328 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 18 hom., cov: 32)

Exomes 𝑓: 0.023 ( 499 hom. )

Consequence

ANKRD26
NM_014915.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:7

Conservation

PhyloP100: 0.465

Publications

5 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 10-27035066-C-T is Benign according to our data. Variant chr10-27035066-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.465 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0147 (2231/152280) while in subpopulation NFE AF = 0.022 (1496/67996). AF 95% confidence interval is 0.0211. There are 18 homozygotes in GnomAd4. There are 1035 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.3384G>A	p.Lys1128Lys	synonymous_variant	Exon 24 of 34	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.3384G>A	p.Lys1128Lys	synonymous_variant	Exon 24 of 34	5	NM_014915.3	ENSP00000365255.4		Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2234

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.0175

AC:

4350

AN:

248588

AF XY:

0.0181

show subpopulations

Gnomad AFR exome

AF:

0.00530

Gnomad AMR exome

AF:

0.00759

Gnomad ASJ exome

AF:

0.0377

Gnomad EAS exome

AF:

0.000278

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0218

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0233

AC:

34081

AN:

1461048

Hom.:

499

Cov.:

AF XY:

0.0233

AC XY:

16903

AN XY:

726800

show subpopulations

African (AFR)

AF:

0.00485

AC:

162

AN:

33404

American (AMR)

AF:

0.00775

AC:

346

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

954

AN:

26090

East Asian (EAS)

AF:

0.000202

AC:

AN:

39678

South Asian (SAS)

AF:

0.0244

AC:

2102

AN:

86088

European-Finnish (FIN)

AF:

0.0132

AC:

701

AN:

53298

Middle Eastern (MID)

AF:

0.0226

AC:

130

AN:

5760

European-Non Finnish (NFE)

AF:

0.0255

AC:

28395

AN:

1111768

Other (OTH)

AF:

0.0213

AC:

1283

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1827

3654

5481

7308

9135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1110

2220

3330

4440

5550

<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:

0.0147

AC:

2231

AN:

152280

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1035

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00486

AC:

202

AN:

41578

American (AMR)

AF:

0.0110

AC:

169

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0211

AC:

102

AN:

4828

European-Finnish (FIN)

AF:

0.0105

AC:

111

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0220

AC:

1496

AN:

67996

Other (OTH)

AF:

0.0166

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

110

219

329

438

548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0201

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0221

EpiControl

AF:

0.0198

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 24, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

Variant was observed in a homozygous state in population databases more than expected for disease.Allele frequency is greater than expected for the disorder.A synonymous variant not located in a splice region.SubpopulationAllele FrequencyAllele NumberHomozygotesEuropean-Non Finnish (NFE)2.1788%112,95234European-Finnish (FIN)1.3103%21,44610Other (OTH)2.0923%6,0222Ashkenazi Jewish (ASJ)3.7685%10,00416African (AFR)0.5299%15,4740East Asian (EAS)0.0278%17,9600South Asian (SAS)2.4931%30,36436American (AMR)0.7595%34,3662 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Thrombocytopenia 2

Benign:3

Jan 13, 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. -

Oct 17, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 06, 2016

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

-0.37

CADD

Benign

5.4

(source)

DANN

Benign

0.56

PhyloP100

0.47

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