rs3737056

Variant names:

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

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.-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

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=-0.51).
• BP6: Variant 10-27100385-C-T is Benign according to our data. Variant chr10-27100385-C-T is described in ClinVar as [Benign]. Clinvar id 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

Gnomad4 AFR exome AF: 0.0142

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0899

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0788

Gnomad4 OTH exome AF: 0.0978

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

Gnomad4 AFR AF: 0.0181

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0830 Hom.: 595

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 10, 2018

GeneDx

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

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. -

Dec 05, 2021

Genome-Nilou Lab

Significance: 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	-0.51
CADD	Benign	7.8
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)		0.0		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: rs3737056; hg19: chr10-27389314;