rs41279942

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014915.3(ANKRD26):c.576G>A(p.Gln192Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,613,338 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.016 ( 246 hom. )

Consequence

ANKRD26
NM_014915.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.919

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-27092468-C-T is Benign according to our data. Variant chr10-27092468-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27092468-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.919 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0131 (1993/152232) while in subpopulation NFE AF= 0.0222 (1508/68000). AF 95% confidence interval is 0.0212. There are 21 homozygotes in gnomad4. There are 969 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1993 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.576G>A	p.Gln192Gln	synonymous_variant	Exon 4 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.576G>A	p.Gln192Gln	synonymous_variant	Exon 4 of 34	5	NM_014915.3	ENSP00000365255.4		Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1994

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00307

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0222

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.0132

AC:

3293

AN:

249020

Hom.:

AF XY:

0.0138

AC XY:

1865

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.00343

Gnomad AMR exome

AF:

0.00354

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00850

Gnomad FIN exome

AF:

0.0167

Gnomad NFE exome

AF:

0.0202

Gnomad OTH exome

AF:

0.0156

GnomAD4 exome

AF:

0.0163

AC:

23770

AN:

1461106

Hom.:

246

Cov.:

AF XY:

0.0164

AC XY:

11886

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.0124

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00881

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0187

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.0131

AC:

1993

AN:

152232

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

969

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00306

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.0222

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.0177

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0167

EpiControl

AF:

0.0163

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Thrombocytopenia 2

Benign:3

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

Aug 13, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 07, 2022

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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