rs78251061

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014915.3(ANKRD26):c.4145T>A(p.Phe1382Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000981 in 1,571,426 control chromosomes in the GnomAD database, including 15 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1382I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0051 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 8 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.05

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, G2P, Ambry Genetics, 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=0.003745854).

BP6

Variant 10-27022628-A-T is Benign according to our data. Variant chr10-27022628-A-T is described in ClinVar as Benign. ClinVar VariationId is 260469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00509 (775/152300) while in subpopulation AFR AF = 0.0178 (738/41564). AF 95% confidence interval is 0.0167. There are 7 homozygotes in GnomAd4. There are 352 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 775 AD gene.

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.4145T>A	p.Phe1382Tyr	missense	Exon 29 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.4142T>A	p.Phe1381Tyr	missense	Exon 29 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.4145T>A	p.Phe1382Tyr	missense	Exon 29 of 34	ENSP00000365255.4	Q9UPS8-1
ANKRD26	ENST00000436985.7	TSL:1	c.4142T>A	p.Phe1381Tyr	missense	Exon 29 of 34	ENSP00000405112.3	E7ESJ3
ANKRD26	ENST00000968143.1		c.5231T>A	p.Phe1744Tyr	missense	Exon 30 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

774

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00122

AC:

302

AN:

247816

AF XY:

0.000863

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000540

AC:

766

AN:

1419126

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

316

AN XY:

706116

show subpopulations

African (AFR)

AF:

0.0199

AC:

646

AN:

32542

American (AMR)

AF:

0.000913

AC:

AN:

43808

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25190

East Asian (EAS)

AF:

0.00

AC:

AN:

38756

South Asian (SAS)

AF:

0.0000470

AC:

AN:

85114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51712

Middle Eastern (MID)

AF:

0.000718

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.00000742

AC:

AN:

1078036

Other (OTH)

AF:

0.00110

AC:

AN:

58398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00509

AC:

775

AN:

152300

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

352

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0178

AC:

738

AN:

41564

American (AMR)

AF:

0.00203

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68012

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00141

Hom.:

Bravo

AF:

0.00601

ESP6500AA

AF:

0.0186

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00152

AC:

183

Asia WGS

AF:

0.000581

AC:

AN:

3458

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Thrombocytopenia 2 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.37

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.96

PhyloP100

2.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

REVEL

Benign

0.093

Sift

Benign

0.066

Sift4G

Uncertain

0.018

Vest4

0.21

MVP

0.44

MPC

0.070

ClinPred

0.0040

GERP RS

3.0

PromoterAI

-0.0070

Neutral

(source)

Varity_R

0.060

gMVP

0.026

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over