chr10-27100466-G-C

Variant names:

• chr10-27100466-G-C
• rs41299222
• NM_014915.3:c.-140C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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=-0.56).
• BP6: Variant 10-27100466-G-C is Benign according to our data. Variant chr10-27100466-G-C is described in ClinVar as Benign. ClinVar VariationId is 260453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.-140C>G		5_prime_UTR_variant	Exon 1 of 34	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.-140C>G		5_prime_UTR_variant	Exon 1 of 34	5	NM_014915.3	ENSP00000365255.4

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

African (AFR) AF: 0.0845 AC: 2177 AN: 25762

American (AMR) AF: 0.0220 AC: 500 AN: 22698

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 1350 AN: 19232

East Asian (EAS) AF: 0.00173 AC: 62 AN: 35814

South Asian (SAS) AF: 0.0301 AC: 1963 AN: 65140

European-Finnish (FIN) AF: 0.0549 AC: 1730 AN: 31524

Middle Eastern (MID) AF: 0.0443 AC: 151 AN: 3406

European-Non Finnish (NFE) AF: 0.0486 AC: 43332 AN: 892268

Other (OTH) AF: 0.0473 AC: 2319 AN: 49034

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

African (AFR) AF: 0.0832 AC: 3460 AN: 41584

American (AMR) AF: 0.0331 AC: 507 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5186

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4832

European-Finnish (FIN) AF: 0.0518 AC: 550 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0516 AC: 3510 AN: 68020

Other (OTH) AF: 0.0426 AC: 90 AN: 2112

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

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

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. -

Oct 17, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

- -

Dec 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.56
CADD	Benign	4.2
DANN	Benign	0.81
PhyloP100		-1.6
PromoterAI		0.54	Over-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=168/132	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41299222; hg19: chr10-27389395;