rs115864032

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014915.3(ANKRD26):c.1207+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 1,610,764 control chromosomes in the GnomAD database, including 1,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 91 hom., cov: 31)

Exomes 𝑓: 0.035 ( 945 hom. )

Consequence

ANKRD26
NM_014915.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.178

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-27067142-T-C is Benign according to our data. Variant chr10-27067142-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27067142-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0334 (5080/152278) while in subpopulation NFE AF= 0.0389 (2644/68024). AF 95% confidence interval is 0.0376. There are 91 homozygotes in gnomad4. There are 2449 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5080 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3 link	c.1207+15A>G		intron_variant	Intron 10 of 33	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.1207+15A>G		intron_variant	Intron 10 of 33	5	NM_014915.3	ENSP00000365255.4		Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5079

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0574

Gnomad EAS

AF:

0.00346

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0389

Gnomad OTH

AF:

0.0325

GnomAD3 exomes

AF:

0.0315

AC:

7838

AN:

249018

Hom.:

153

AF XY:

0.0317

AC XY:

4290

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.0575

Gnomad EAS exome

AF:

0.00389

Gnomad SAS exome

AF:

0.0272

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.0383

Gnomad OTH exome

AF:

0.0332

GnomAD4 exome

AF:

0.0349

AC:

50924

AN:

1458486

Hom.:

945

Cov.:

AF XY:

0.0349

AC XY:

25293

AN XY:

725708

show subpopulations

Gnomad4 AFR exome

AF:

0.0300

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0577

Gnomad4 EAS exome

AF:

0.00229

Gnomad4 SAS exome

AF:

0.0281

Gnomad4 FIN exome

AF:

0.0417

Gnomad4 NFE exome

AF:

0.0367

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0334

AC:

5080

AN:

152278

Hom.:

Cov.:

AF XY:

0.0329

AC XY:

2449

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0291

Gnomad4 AMR

AF:

0.0245

Gnomad4 ASJ

AF:

0.0574

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.0389

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0399

Hom.:

Bravo

AF:

0.0319

Asia WGS

AF:

0.0250

AC:

AN:

3478

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

Oct 17, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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. -

Dec 05, 2021

Genome-Nilou Lab

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 08, 2018

GeneDx

Significance: Likely 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

-0.88

CADD

Benign

2.6

DANN

Benign

0.54

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