10-27092420-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014915.3(ANKRD26):c.624A>G(p.Val208=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,607,082 control chromosomes in the GnomAD database, including 38,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4875 hom., cov: 32)
  • Exomes 𝑓: 0.20 (33778 hom.)
• Consequence: ANKRD26 NM_014915.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.38

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 10-27092420-T-C is Benign according to our data. Variant chr10-27092420-T-C is described in ClinVar as [Benign]. Clinvar id is 260473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD26	NM_014915.3	c.624A>G	p.Val208=	synonymous_variant	4/34	ENST00000376087.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD26	ENST00000376087.5	c.624A>G	p.Val208=	synonymous_variant	4/34	5	NM_014915.3	A2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35778 AN: 151946 Hom.: 4853 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.242 AC: 59829 AN: 247536 Hom.: 8759 AF XY: 0.244 AC XY: 32849 AN XY: 134438

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.549

Gnomad SAS exome AF: 0.372

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.195 AC: 284013 AN: 1455018 Hom.: 33778 Cov.: 31 AF XY: 0.199 AC XY: 144413 AN XY: 724138

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.578

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.236 AC: 35847 AN: 152064 Hom.: 4875 Cov.: 32 AF XY: 0.245 AC XY: 18188 AN XY: 74342

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.233

Alfa AF: 0.179 Hom.: 6406

Bravo AF: 0.232

Asia WGS AF: 0.465 AC: 1615 AN: 3478

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	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	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 18, 2023	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -

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	-1.0
Cadd	Benign	0.20
Dann	Benign	0.52

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: rs2297145; hg19: chr10-27381349;