rs41299222

Positions:

• chr10-27100466-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014915.3(ANKRD26):​c.-140C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,297,204 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (267 hom., cov: 34)
  • Exomes 𝑓: 0.047 (1417 hom.)
• Consequence: ANKRD26 NM_014915.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.58

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 10-27100466-G-C is Benign according to our data. Variant chr10-27100466-G-C is described in ClinVar as [Benign]. Clinvar id is 260453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27100466-G-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.-140C>G		5_prime_UTR_variant	1/34	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.-140C>G		5_prime_UTR_variant	1/34	5	NM_014915.3	ENSP00000365255	A2
ANKRD26	ENST00000436985.7	c.-140C>G		5_prime_UTR_variant	1/34	1		ENSP00000405112	P4
ANKRD26	ENST00000676420.1	c.-140C>G		5_prime_UTR_variant, NMD_transcript_variant	1/25			ENSP00000502355

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8524 AN: 152208 Hom.: 265 Cov.: 34

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0431

GnomAD4 exome AF: 0.0468 AC: 53584 AN: 1144878 Hom.: 1417 Cov.: 15 AF XY: 0.0463 AC XY: 26376 AN XY: 569224

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.0220

Gnomad4 ASJ exome AF: 0.0702

Gnomad4 EAS exome AF: 0.00173

Gnomad4 SAS exome AF: 0.0301

Gnomad4 FIN exome AF: 0.0549

Gnomad4 NFE exome AF: 0.0486

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0561 AC: 8540 AN: 152326 Hom.: 267 Cov.: 34 AF XY: 0.0549 AC XY: 4089 AN XY: 74484

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0516

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0614 Hom.: 40

Bravo AF: 0.0564

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Thrombocytopenia 2 Benign:4

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
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. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 18, 2023	- -

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	Dec 26, 2018	This variant is associated with the following publications: (PMID: 28277066, 29545013, 25902755) -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.2
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs41299222; hg19: chr10-27389395;