rs75445709

chr10-27038058-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_014915.3(ANKRD26):c.2376-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,605,426 control chromosomes in the GnomAD database, including 225 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (117 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (108 hom.)
• Consequence: ANKRD26 NM_014915.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001268
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.566

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 10-27038058-C-T is Benign according to our data. Variant chr10-27038058-C-T is described in ClinVar as [Benign]. Clinvar id is 260462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD26	NM_014915.3	c.2376-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000376087.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD26	ENST00000376087.5	c.2376-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_014915.3	A2

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3172 AN: 152044 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0729

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00537 AC: 1314 AN: 244792 Hom.: 38 AF XY: 0.00417 AC XY: 555 AN XY: 133128

Gnomad AFR exome AF: 0.0761

Gnomad AMR exome AF: 0.00268

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.000447

Gnomad SAS exome AF: 0.000230

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000196

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00216 AC: 3140 AN: 1453264 Hom.: 108 Cov.: 30 AF XY: 0.00188 AC XY: 1361 AN XY: 723296

Gnomad4 AFR exome AF: 0.0778

Gnomad4 AMR exome AF: 0.00314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.000221

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000721

Gnomad4 OTH exome AF: 0.00473

GnomAD4 genome AF: 0.0209 AC: 3174 AN: 152162 Hom.: 117 Cov.: 32 AF XY: 0.0200 AC XY: 1485 AN XY: 74402

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00615 Hom.: 11

Bravo AF: 0.0240

Asia WGS AF: 0.00145 AC: 5 AN: 3470

EpiCase AF: 0.000109

EpiControl AF: 0.000298

ClinVar

Significance: 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 13, 2023	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2019	- -

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	-0.41
Cadd	Benign	8.8
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.046
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: rs75445709; hg19: chr10-27326987;