rs115864032

Positions:

• chr10-27067142-T-C
• chr10-27067142-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.178

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=-0.88).
• 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/exons	MANE	UniProt
ANKRD26	NM_014915.3	c.1207+15A>G		intron_variant		ENST00000376087.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD26	ENST00000376087.5	c.1207+15A>G		intron_variant		5	NM_014915.3	A2

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5079 AN: 152160 Hom.: 91 Cov.: 31

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

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.: 31 AF XY: 0.0349 AC XY: 25293 AN XY: 725708

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.: 91 Cov.: 31 AF XY: 0.0329 AC XY: 2449 AN XY: 74476

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.: 24

Bravo AF: 0.0319

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Thrombocytopenia 2 Benign:3

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:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

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	-0.88
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

Other links and lift over

dbSNP: rs115864032; hg19: chr10-27356071;