10-27005520-CAT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_014915.3(ANKRD26):c.*68_*69del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 1,558,240 control chromosomes in the GnomAD database, including 8,120 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (780 hom., cov: 31)
  • Exomes 𝑓: 0.093 (7340 hom.)
• Consequence: ANKRD26 NM_014915.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0810

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 -16 ACMG points.

• BP6: Variant 10-27005520-CAT-C is Benign according to our data. Variant chr10-27005520-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 299724.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	UniProt
ANKRD26	NM_014915.3	c.*68_*69del		3_prime_UTR_variant	34/34	ENST00000376087.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD26	ENST00000376087.5	c.*68_*69del		3_prime_UTR_variant	34/34	5	NM_014915.3	A2

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14082 AN: 151982 Hom.: 767 Cov.: 31

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.0990

GnomAD4 exome AF: 0.0926 AC: 130234 AN: 1406138 Hom.: 7340 AF XY: 0.0937 AC XY: 65633 AN XY: 700150

Gnomad4 AFR exome AF: 0.0579

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0809

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0928 AC: 14118 AN: 152102 Hom.: 780 Cov.: 31 AF XY: 0.0987 AC XY: 7335 AN XY: 74322

Gnomad4 AFR AF: 0.0578

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: 0.0847

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0812 Hom.: 93

Bravo AF: 0.0891

Asia WGS AF: 0.241 AC: 834 AN: 3468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Thrombocytopenia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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: rs3215884; hg19: chr10-27294449;