rs41279942

chr10-27092468-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014915.3(ANKRD26):c.576G>A(p.Gln192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,613,338 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (21 hom., cov: 32)
  • Exomes 𝑓: 0.016 (246 hom.)
• Consequence: ANKRD26 NM_014915.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.919

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=-0.86).
• BP6: Variant 10-27092468-C-T is Benign according to our data. Variant chr10-27092468-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27092468-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.919 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0131 (1993/152232) while in subpopulation NFE AF= 0.0222 (1508/68000). AF 95% confidence interval is 0.0212. There are 21 homozygotes in gnomad4. There are 969 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1994 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD26	NM_014915.3	c.576G>A	p.Gln192=	synonymous_variant	4/34	ENST00000376087.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD26	ENST00000376087.5	c.576G>A	p.Gln192=	synonymous_variant	4/34	5	NM_014915.3	A2

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1994 AN: 152114 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.0132 AC: 3293 AN: 249020 Hom.: 38 AF XY: 0.0138 AC XY: 1865 AN XY: 135136

Gnomad AFR exome AF: 0.00343

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00850

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.0202

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0163 AC: 23770 AN: 1461106 Hom.: 246 Cov.: 31 AF XY: 0.0164 AC XY: 11886 AN XY: 726862

Gnomad4 AFR exome AF: 0.00239

Gnomad4 AMR exome AF: 0.00371

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00881

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.0187

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0131 AC: 1993 AN: 152232 Hom.: 21 Cov.: 32 AF XY: 0.0130 AC XY: 969 AN XY: 74432

Gnomad4 AFR AF: 0.00306

Gnomad4 AMR AF: 0.00419

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0169

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.0177 Hom.: 11

Bravo AF: 0.0111

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0167

EpiControl AF: 0.0163

ClinVar

Significance: Benign/Likely 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	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 21, 2023	- -
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 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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 07, 2022	- -

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	-0.86
Cadd	Benign	1.8
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41279942; hg19: chr10-27381397;