rs41299210

Positions:

chr10-27035066-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_014915.3(ANKRD26):c.3384G>A(p.Lys1128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,613,328 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 18 hom., cov: 32)

Exomes 𝑓: 0.023 ( 499 hom. )

Consequence

ANKRD26
NM_014915.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: 0.465

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 10-27035066-C-T is Benign according to our data. Variant chr10-27035066-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.465 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0147 (2231/152280) while in subpopulation NFE AF= 0.022 (1496/67996). AF 95% confidence interval is 0.0211. There are 18 homozygotes in gnomad4. There are 1035 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD26	NM_014915.3 linkuse as main transcript	c.3384G>A	p.Lys1128=	synonymous_variant	24/34	ENST00000376087.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD26	ENST00000376087.5 linkuse as main transcript	c.3384G>A	p.Lys1128=	synonymous_variant	24/34	5	NM_014915.3	A2	Q9UPS8-1
ANKRD26	ENST00000436985.7 linkuse as main transcript	c.3381G>A	p.Lys1127=	synonymous_variant	24/34	1		P4
ANKRD26	ENST00000675349.1 linkuse as main transcript	n.3113G>A		non_coding_transcript_exon_variant	9/9
ANKRD26	ENST00000675116.1 linkuse as main transcript	c.1035G>A	p.Lys345=	synonymous_variant, NMD_transcript_variant	4/15

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2234

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0220

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0175

AC:

4350

AN:

248588

Hom.:

AF XY:

0.0181

AC XY:

2440

AN XY:

134854

show subpopulations

Gnomad AFR exome

AF:

0.00530

Gnomad AMR exome

AF:

0.00759

Gnomad ASJ exome

AF:

0.0377

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.0249

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.0218

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0233

AC:

34081

AN:

1461048

Hom.:

499

Cov.:

AF XY:

0.0233

AC XY:

16903

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.00485

Gnomad4 AMR exome

AF:

0.00775

Gnomad4 ASJ exome

AF:

0.0366

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0244

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.0255

Gnomad4 OTH exome

AF:

0.0213

GnomAD4 genome

AF:

0.0147

AC:

2231

AN:

152280

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1035

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0311

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0211

Gnomad4 FIN

AF:

0.0105

Gnomad4 NFE

AF:

0.0220

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0221

EpiControl

AF:

0.0198

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Uncertain significance, no assertion criteria provided	clinical testing	Department of Pathology and Laboratory Medicine, Sinai Health System	-	Variant was observed in a homozygous state in population databases more than expected for disease.Allele frequency is greater than expected for the disorder.A synonymous variant not located in a splice region.SubpopulationAllele FrequencyAllele NumberHomozygotesEuropean-Non Finnish (NFE)2.1788%112,95234European-Finnish (FIN)1.3103%21,44610Other (OTH)2.0923%6,0222Ashkenazi Jewish (ASJ)3.7685%10,00416African (AFR)0.5299%15,4740East Asian (EAS)0.0278%17,9600South Asian (SAS)2.4931%30,36436American (AMR)0.7595%34,3662 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2020	- -

Thrombocytopenia 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 17, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

5.4

DANN

Benign

0.56

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