10-27004378-C-T

Position:

• chr10-27004378-C-T

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.*1212G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 151,798 control chromosomes in the GnomAD database, including 791 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (791 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ANKRD26 NM_014915.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.32

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=-0.92).
• BP6: Variant 10-27004378-C-T is Benign according to our data. Variant chr10-27004378-C-T is described in ClinVar as [Benign]. Clinvar id is 299711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD26	NM_014915.3	c.*1212G>A		3_prime_UTR_variant	34/34	ENST00000376087.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD26	ENST00000376087.5	c.*1212G>A		3_prime_UTR_variant	34/34	5	NM_014915.3	A2

Frequencies

GnomAD3 genomes AF: 0.0936 AC: 14195 AN: 151682 Hom.: 777 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.101

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0938 AC: 14238 AN: 151798 Hom.: 791 Cov.: 32 AF XY: 0.0996 AC XY: 7384 AN XY: 74156

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.0847

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0825 Hom.: 146

Bravo AF: 0.0900

Asia WGS AF: 0.242 AC: 839 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Thrombocytopenia 2 Benign:1

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.20

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: rs66931439; hg19: chr10-27293307;