rs66931439

Variant names:

• chr10-27004378-C-T
• rs66931439
• NM_014915.3:c.*1212G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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.*1212G>A		3_prime_UTR	Exon 34 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.*1212G>A		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.*1212G>A		3_prime_UTR	Exon 34 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000968139.1		c.*1212G>A		3_prime_UTR	Exon 33 of 33	ENSP00000638198.1
	ANKRD26	ENST00000676280.1		c.*1212G>A		3_prime_UTR	Exon 4 of 4	ENSP00000502438.1	A0A6Q8PGV3

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

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

African (AFR) AF: 0.0607 AC: 2512 AN: 41396

American (AMR) AF: 0.118 AC: 1797 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3460

East Asian (EAS) AF: 0.281 AC: 1447 AN: 5154

South Asian (SAS) AF: 0.157 AC: 754 AN: 4798

European-Finnish (FIN) AF: 0.125 AC: 1321 AN: 10530

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0847 AC: 5752 AN: 67924

Other (OTH) AF: 0.111 AC: 232 AN: 2098

Alfa AF: 0.0816 Hom.: 147

Bravo AF: 0.0900

Asia WGS AF: 0.242 AC: 839 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Thrombocytopenia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.20
PhyloP100		-1.3
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: rs66931439; hg19: chr10-27293307;