rs12359281

Positions:

chr10-27064078-T-C

Variant summary

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

The NM_014915.3(ANKRD26):c.1273A>G(p.Ile425Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,605,428 control chromosomes in the GnomAD database, including 1,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 207 hom., cov: 32)

Exomes 𝑓: 0.026 ( 827 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.467

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=0.0012910664).

BP6

Variant 10-27064078-T-C is Benign according to our data. Variant chr10-27064078-T-C is described in ClinVar as [Benign]. Clinvar id is 260457.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27064078-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD26	NM_014915.3 linkuse as main transcript	c.1273A>G	p.Ile425Val	missense_variant	12/34	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5 linkuse as main transcript	c.1273A>G	p.Ile425Val	missense_variant	12/34	5	NM_014915.3	ENSP00000365255	A2	Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.0424

AC:

6443

AN:

151978

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0865

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0588

Gnomad FIN

AF:

0.0244

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0179

Gnomad OTH

AF:

0.0422

GnomAD3 exomes

AF:

0.0362

AC:

8955

AN:

247414

Hom.:

284

AF XY:

0.0362

AC XY:

4863

AN XY:

134412

show subpopulations

Gnomad AFR exome

AF:

0.0858

Gnomad AMR exome

AF:

0.0246

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.0590

Gnomad FIN exome

AF:

0.0246

Gnomad NFE exome

AF:

0.0186

Gnomad OTH exome

AF:

0.0282

GnomAD4 exome

AF:

0.0257

AC:

37363

AN:

1453332

Hom.:

827

Cov.:

AF XY:

0.0268

AC XY:

19373

AN XY:

723500

show subpopulations

Gnomad4 AFR exome

AF:

0.0835

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.0592

Gnomad4 FIN exome

AF:

0.0291

Gnomad4 NFE exome

AF:

0.0183

Gnomad4 OTH exome

AF:

0.0318

GnomAD4 genome

AF:

0.0424

AC:

6448

AN:

152096

Hom.:

207

Cov.:

AF XY:

0.0421

AC XY:

3127

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0864

Gnomad4 AMR

AF:

0.0171

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0584

Gnomad4 FIN

AF:

0.0244

Gnomad4 NFE

AF:

0.0179

Gnomad4 OTH

AF:

0.0423

Alfa

AF:

0.0246

Hom.:

111

Bravo

AF:

0.0438

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.0891

AC:

318

ESP6500EA

AF:

0.0202

AC:

164

ExAC

AF:

0.0374

AC:

4510

Asia WGS

AF:

0.0660

AC:

230

AN:

3466

EpiCase

AF:

0.0182

EpiControl

AF:

0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Thrombocytopenia 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

DANN

Benign

0.30

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.062

Sift

Benign

0.35

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0010

.;B

Vest4

0.018

MPC

0.045

ClinPred

0.00045

GERP RS

-2.8

Varity_R

0.045

gMVP

0.0073

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