NM_014915.3:c.*815dupT

Variant names:

• chr10-27004774-G-GA
• rs397845107
• NM_014915.3:c.*815dupT

Variant summary

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

The NM_014915.3(ANKRD26):​c.*815dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,500 control chromosomes in the GnomAD database, including 1,151 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1150 hom., cov: 31)
  • Exomes 𝑓: 0.070 (1 hom.)
• Consequence: ANKRD26 NM_014915.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00600
• Publications: 0 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 10-27004774-G-GA is Benign according to our data. Variant chr10-27004774-G-GA is described in ClinVar as Likely_benign. ClinVar VariationId is 299718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 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.*815dupT		3_prime_UTR	Exon 34 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.*815dupT		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.*815dupT		3_prime_UTR	Exon 34 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000968139.1		c.*815dupT		3_prime_UTR	Exon 33 of 33	ENSP00000638198.1
	ANKRD26	ENST00000676280.1		c.*815dupT		3_prime_UTR	Exon 4 of 4	ENSP00000502438.1	A0A6Q8PGV3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16119 AN: 152026 Hom.: 1148 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0933

GnomAD4 exome AF: 0.0698 AC: 25 AN: 358 Hom.: 1 Cov.: 2 AF XY: 0.0688 AC XY: 11 AN XY: 160

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0680 AC: 23 AN: 338

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.106 AC: 16141 AN: 152142 Hom.: 1150 Cov.: 31 AF XY: 0.110 AC XY: 8206 AN XY: 74358

African (AFR) AF: 0.164 AC: 6826 AN: 41518

American (AMR) AF: 0.0610 AC: 932 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 299 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1429 AN: 5172

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4818

European-Finnish (FIN) AF: 0.119 AC: 1256 AN: 10576

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0597 AC: 4057 AN: 67990

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0864 Hom.: 76

Bravo AF: 0.103

Asia WGS AF: 0.215 AC: 745 AN: 3478

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		0.0060
Mutation Taster		=100/0	polymorphism (auto)

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: rs397845107; hg19: chr10-27293703;