10-27100385-C-T

Variant names:

• chr10-27100385-C-T
• rs3737056
• NM_014915.3:c.-59G>A

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.-59G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 1,596,866 control chromosomes in the GnomAD database, including 7,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (702 hom., cov: 34)
  • Exomes 𝑓: 0.089 (7261 hom.)
• Consequence: ANKRD26 NM_014915.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.943
• Publications: 15 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=-0.51).
• BP6: Variant 10-27100385-C-T is Benign according to our data. Variant chr10-27100385-C-T is described in ClinVar as Benign. ClinVar VariationId is 260454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.-59G>A		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.-59G>A		5_prime_UTR_variant	Exon 1 of 34	5	NM_014915.3	ENSP00000365255.4

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12113 AN: 152170 Hom.: 690 Cov.: 34

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.0903

GnomAD4 exome AF: 0.0894 AC: 129089 AN: 1444576 Hom.: 7261 Cov.: 34 AF XY: 0.0907 AC XY: 65235 AN XY: 719006

African (AFR) AF: 0.0142 AC: 471 AN: 33218

American (AMR) AF: 0.107 AC: 4735 AN: 44064

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 2340 AN: 26016

East Asian (EAS) AF: 0.276 AC: 10929 AN: 39656

South Asian (SAS) AF: 0.143 AC: 12178 AN: 85314

European-Finnish (FIN) AF: 0.111 AC: 4613 AN: 41610

Middle Eastern (MID) AF: 0.0975 AC: 402 AN: 4122

European-Non Finnish (NFE) AF: 0.0788 AC: 87560 AN: 1110622

Other (OTH) AF: 0.0978 AC: 5861 AN: 59954

GnomAD4 genome AF: 0.0797 AC: 12139 AN: 152290 Hom.: 702 Cov.: 34 AF XY: 0.0864 AC XY: 6435 AN XY: 74474

African (AFR) AF: 0.0181 AC: 753 AN: 41576

American (AMR) AF: 0.111 AC: 1704 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0881 AC: 306 AN: 3472

East Asian (EAS) AF: 0.282 AC: 1454 AN: 5162

South Asian (SAS) AF: 0.155 AC: 749 AN: 4824

European-Finnish (FIN) AF: 0.127 AC: 1352 AN: 10610

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5537 AN: 68022

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.0790 Hom.: 715

Bravo AF: 0.0739

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Thrombocytopenia 2 Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 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. -

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	-0.51
CADD	Benign	7.8
DANN	Benign	0.81
PhyloP100		-0.94
PromoterAI		-0.088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=182/118	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: rs3737056; hg19: chr10-27389314;