rs72807627

Positions:

• chr10-27028849-T-C

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.3972+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 1,607,462 control chromosomes in the GnomAD database, including 8,403 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 0.093 (790 hom., cov: 32)
  • Exomes 𝑓: 0.092 (7613 hom.)
• Consequence: ANKRD26 NM_014915.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002748
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.405

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=-0.54).
• BP6: Variant 10-27028849-T-C is Benign according to our data. Variant chr10-27028849-T-C is described in ClinVar as [Benign]. Clinvar id is 260468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.3972+3A>G		splice_region_variant, intron_variant		ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.3972+3A>G		splice_region_variant, intron_variant		5	NM_014915.3	ENSP00000365255.4
ANKRD26	ENST00000436985.7	c.3969+3A>G		splice_region_variant, intron_variant		1		ENSP00000405112.3
ANKRD26	ENST00000675116.1	n.*295+3A>G		splice_region_variant, intron_variant				ENSP00000501975.1
ANKRD26	ENST00000675936.1	n.387+3A>G		splice_region_variant, intron_variant				ENSP00000502093.1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14123 AN: 152046 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0998

GnomAD3 exomes AF: 0.113 AC: 28190 AN: 248670 Hom.: 2060 AF XY: 0.114 AC XY: 15443 AN XY: 134944

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.291

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0848

Gnomad OTH exome AF: 0.0969

GnomAD4 exome AF: 0.0921 AC: 134084 AN: 1455298 Hom.: 7613 Cov.: 31 AF XY: 0.0934 AC XY: 67616 AN XY: 724218

Gnomad4 AFR exome AF: 0.0582

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0931 AC: 14159 AN: 152164 Hom.: 790 Cov.: 32 AF XY: 0.0990 AC XY: 7365 AN XY: 74402

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0845

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0821 Hom.: 301

Bravo AF: 0.0894

Asia WGS AF: 0.240 AC: 834 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:7

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 13, 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	Aug 21, 2023	- -

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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	-0.54
CADD	Benign	12
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.060		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: rs72807627; hg19: chr10-27317778; COSMIC: COSV65775812;