rs138423863

Positions:

• chr10-27053356-CTCT-C
• chr10-27053356-CTCT-CTCTTCT

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_014915.3(ANKRD26):​c.1596_1598del​(p.Glu533del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,611,050 control chromosomes in the GnomAD database, including 1,828 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (150 hom., cov: 32)
  • Exomes 𝑓: 0.017 (1678 hom.)
• Consequence: ANKRD26 NM_014915.3 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.70

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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_014915.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-27053356-CTCT-C is Benign according to our data. Variant chr10-27053356-CTCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 260460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27053356-CTCT-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.1596_1598del	p.Glu533del	inframe_deletion	16/34	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.1596_1598del	p.Glu533del	inframe_deletion	16/34	5	NM_014915.3	ENSP00000365255	A2

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2748 AN: 152014 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.0362 AC: 8988 AN: 248570 Hom.: 481 AF XY: 0.0393 AC XY: 5300 AN XY: 134958

Gnomad AFR exome AF: 0.00757

Gnomad AMR exome AF: 0.0293

Gnomad ASJ exome AF: 0.00954

Gnomad EAS exome AF: 0.143

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.0570

Gnomad NFE exome AF: 0.00350

Gnomad OTH exome AF: 0.0256

GnomAD4 exome AF: 0.0171 AC: 24910 AN: 1458918 Hom.: 1678 AF XY: 0.0198 AC XY: 14393 AN XY: 725792

Gnomad4 AFR exome AF: 0.00754

Gnomad4 AMR exome AF: 0.0272

Gnomad4 ASJ exome AF: 0.00992

Gnomad4 EAS exome AF: 0.204

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0524

Gnomad4 NFE exome AF: 0.00141

Gnomad4 OTH exome AF: 0.0196

GnomAD4 genome AF: 0.0181 AC: 2749 AN: 152132 Hom.: 150 Cov.: 32 AF XY: 0.0235 AC XY: 1750 AN XY: 74360

Gnomad4 AFR AF: 0.00744

Gnomad4 AMR AF: 0.0139

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.00268

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00903 Hom.: 7

Bravo AF: 0.0131

Asia WGS AF: 0.121 AC: 417 AN: 3466

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Sep 26, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 02, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Thrombocytopenia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Thrombocytopenia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs138423863; hg19: chr10-27342285;