rs10829163

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014915.3(ANKRD26):c.3913G>A(p.Val1305Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,610,364 control chromosomes in the GnomAD database, including 31,558 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3634 hom., cov: 32)

Exomes 𝑓: 0.17 ( 27924 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.89

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.16597E-5).

BP6

Variant 10-27028911-C-T is Benign according to our data. Variant chr10-27028911-C-T is described in ClinVar as [Benign]. Clinvar id is 260467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.3913G>A	p.Val1305Ile	missense_variant	Exon 27 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.3913G>A	p.Val1305Ile	missense_variant	Exon 27 of 34	5	NM_014915.3	ENSP00000365255.4		Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30319

AN:

151882

Hom.:

3616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.557

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.194

GnomAD3 exomes

AF:

0.220

AC:

54765

AN:

248564

Hom.:

7686

AF XY:

0.224

AC XY:

30183

AN XY:

134860

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.550

Gnomad SAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.172

AC:

251471

AN:

1458364

Hom.:

27924

Cov.:

AF XY:

0.177

AC XY:

128525

AN XY:

725572

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.343

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.200

AC:

30386

AN:

152000

Hom.:

3634

Cov.:

AF XY:

0.210

AC XY:

15598

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.244

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.161

Hom.:

5973

Bravo

AF:

0.193

TwinsUK

AF:

0.150

AC:

555

ALSPAC

AF:

0.139

AC:

534

ESP6500AA

AF:

0.233

AC:

839

ESP6500EA

AF:

0.145

AC:

1180

ExAC

AF:

0.222

AC:

26746

Asia WGS

AF:

0.456

AC:

1577

AN:

3464

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. -

Nov 22, 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 provided

Benign:3

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 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

- -

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

0.066

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.14

DANN

Benign

0.11

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.11

T;T

MetaRNN

Benign

0.000032

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

0.040

N;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.033

MPC

0.041

ClinPred

0.0013

GERP RS

-4.4

Varity_R

0.014

gMVP

0.011

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over