rs61745662

Positions:

chr10-27035472-T-G

Variant summary

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

The NM_014915.3(ANKRD26):c.2978A>C(p.Glu993Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00417 in 1,614,024 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 133 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 130 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.45

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:

ANKRD26 (HGNC:):

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=0.002908945).

BP6

Variant 10-27035472-T-G is Benign according to our data. Variant chr10-27035472-T-G is described in ClinVar as [Benign]. Clinvar id is 260464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 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.2978A>C	p.Glu993Ala	missense_variant	24/34	ENST00000376087.5	NP_055730.2	Q9UPS8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD26	ENST00000376087.5 linkuse as main transcript	c.2978A>C	p.Glu993Ala	missense_variant	24/34	5	NM_014915.3	ENSP00000365255.4	Q9UPS8-1
ANKRD26	ENST00000436985.7 linkuse as main transcript	c.2975A>C	p.Glu992Ala	missense_variant	24/34	1		ENSP00000405112.3	E7ESJ3
ANKRD26	ENST00000675116.1 linkuse as main transcript	n.626A>C		non_coding_transcript_exon_variant	4/15			ENSP00000501975.1	A0A6Q8PFU2
ANKRD26	ENST00000675349.1 linkuse as main transcript	n.2707A>C		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3346

AN:

152130

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0769

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00555

AC:

1385

AN:

249442

Hom.:

AF XY:

0.00427

AC XY:

578

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.0806

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00231

AC:

3382

AN:

1461776

Hom.:

130

Cov.:

AF XY:

0.00198

AC XY:

1437

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0838

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000764

Gnomad4 OTH exome

AF:

0.00513

GnomAD4 genome

AF:

0.0220

AC:

3348

AN:

152248

Hom.:

133

Cov.:

AF XY:

0.0212

AC XY:

1579

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0767

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00383

Hom.:

Bravo

AF:

0.0254

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0741

AC:

279

ESP6500EA

AF:

0.000607

AC:

ExAC

AF:

0.00645

AC:

779

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombocytopenia 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2023	- -
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 provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2019	- -

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

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.2

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.18

Sift

Benign

0.051

T;T

Sift4G

Uncertain

0.017

D;D

Vest4

0.33

MVP

0.41

MPC

0.23

ClinPred

0.028

GERP RS

5.6

Varity_R

0.31

gMVP

0.088

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