rs115864032

Variant names:

• chr10-27067142-T-C
• rs115864032
• NM_014915.3:c.1207+15A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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:7
• Conservation: PhyloP100: 0.178
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• thrombocytopenia 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• autosomal thrombocytopenia with normal platelets

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 260455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• 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	c.1207+15A>G		intron_variant	Intron 10 of 33	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.1207+15A>G		intron_variant	Intron 10 of 33	5	NM_014915.3	ENSP00000365255.4

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

GnomAD2 exomes AF: 0.0315 AC: 7838 AN: 249018 AF XY: 0.0317

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 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

African (AFR) AF: 0.0300 AC: 1003 AN: 33416

American (AMR) AF: 0.0152 AC: 681 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 1507 AN: 26106

East Asian (EAS) AF: 0.00229 AC: 91 AN: 39664

South Asian (SAS) AF: 0.0281 AC: 2418 AN: 86190

European-Finnish (FIN) AF: 0.0417 AC: 2201 AN: 52830

Middle Eastern (MID) AF: 0.0347 AC: 185 AN: 5338

European-Non Finnish (NFE) AF: 0.0367 AC: 40705 AN: 1109980

Other (OTH) AF: 0.0354 AC: 2133 AN: 60250

GnomAD4 genome AF: 0.0334 AC: 5080 AN: 152278 Hom.: 91 Cov.: 31 AF XY: 0.0329 AC XY: 2449 AN XY: 74476

African (AFR) AF: 0.0291 AC: 1208 AN: 41558

American (AMR) AF: 0.0245 AC: 375 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 199 AN: 3464

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4820

European-Finnish (FIN) AF: 0.0395 AC: 419 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2644 AN: 68024

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0396 Hom.: 25

Bravo AF: 0.0319

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs115864032; hg19: chr10-27356071;