chr10-27060339-A-G

Position:

chr10-27060339-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014915.3(ANKRD26):c.1564+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,595,366 control chromosomes in the GnomAD database, including 428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 32 hom., cov: 32)

Exomes 𝑓: 0.022 ( 396 hom. )

Consequence

ANKRD26
NM_014915.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.03147

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.601

Variant links:

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]

ANKRD26 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-27060339-A-G is Benign according to our data. Variant chr10-27060339-A-G is described in ClinVar as [Benign]. Clinvar id is 260459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27060339-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0169 (2573/152266) while in subpopulation NFE AF= 0.0256 (1739/68020). AF 95% confidence interval is 0.0246. There are 32 homozygotes in gnomad4. There are 1210 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2573 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD26	NM_014915.3 linkuse as main transcript	c.1564+6T>C		splice_donor_region_variant, intron_variant		ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5 linkuse as main transcript	c.1564+6T>C		splice_donor_region_variant, intron_variant		5	NM_014915.3	ENSP00000365255	A2	Q9UPS8-1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2573

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00398

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0186

AC:

4636

AN:

249110

Hom.:

AF XY:

0.0187

AC XY:

2532

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.00323

Gnomad AMR exome

AF:

0.00615

Gnomad ASJ exome

AF:

0.0295

Gnomad EAS exome

AF:

0.00261

Gnomad SAS exome

AF:

0.0131

Gnomad FIN exome

AF:

0.0280

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.0220

AC:

31725

AN:

1443100

Hom.:

396

Cov.:

AF XY:

0.0219

AC XY:

15746

AN XY:

719056

show subpopulations

Gnomad4 AFR exome

AF:

0.00285

Gnomad4 AMR exome

AF:

0.00703

Gnomad4 ASJ exome

AF:

0.0286

Gnomad4 EAS exome

AF:

0.00119

Gnomad4 SAS exome

AF:

0.0142

Gnomad4 FIN exome

AF:

0.0282

Gnomad4 NFE exome

AF:

0.0242

Gnomad4 OTH exome

AF:

0.0208

GnomAD4 genome

AF:

0.0169

AC:

2573

AN:

152266

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1210

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00397

Gnomad4 AMR

AF:

0.0117

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0258

Gnomad4 NFE

AF:

0.0256

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0147

Asia WGS

AF:

0.0160

AC:

AN:

3474

EpiCase

AF:

0.0248

EpiControl

AF:

0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Thrombocytopenia 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 18, 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:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 18, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.5

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.031

dbscSNV1_RF

Benign

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over