rs112091269

Variant names:

• chr10-27004354-CA-C
• rs112091269
• NM_014915.3:c.*1235delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014915.3(ANKRD26):​c.*1235delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 151,908 control chromosomes in the GnomAD database, including 786 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (786 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ANKRD26 NM_014915.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.501
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• thrombocytopenia 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• autosomal thrombocytopenia with normal platelets

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-27004354-CA-C is Benign according to our data. Variant chr10-27004354-CA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 299710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014915.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD26	NM_014915.3	MANE Select	c.*1235delT		3_prime_UTR	Exon 34 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.*1235delT		3_prime_UTR	Exon 34 of 34	NP_001242982.1	E7ESJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD26	ENST00000376087.5	TSL:5 MANE Select	c.*1235delT		3_prime_UTR	Exon 34 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000968139.1		c.*1235delT		3_prime_UTR	Exon 33 of 33	ENSP00000638198.1
	ANKRD26	ENST00000676280.1		c.*1235delT		3_prime_UTR	Exon 4 of 4	ENSP00000502438.1	A0A6Q8PGV3

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14187 AN: 151792 Hom.: 772 Cov.: 31

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: 0.157

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.101

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0937 AC: 14230 AN: 151908 Hom.: 786 Cov.: 31 AF XY: 0.0995 AC XY: 7386 AN XY: 74238

African (AFR) AF: 0.0607 AC: 2515 AN: 41438

American (AMR) AF: 0.118 AC: 1801 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3464

East Asian (EAS) AF: 0.280 AC: 1441 AN: 5150

South Asian (SAS) AF: 0.156 AC: 750 AN: 4804

European-Finnish (FIN) AF: 0.125 AC: 1319 AN: 10512

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.0846 AC: 5748 AN: 67958

Other (OTH) AF: 0.111 AC: 234 AN: 2106

Alfa AF: 0.0285 Hom.: 22

Bravo AF: 0.0899

Asia WGS AF: 0.242 AC: 838 AN: 3474

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs112091269; hg19: chr10-27293283;