10-27061127-G-T

Variant names:

• chr10-27061127-G-T
• rs11015496
• NM_014915.3:c.1462+17C>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.1462+17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,527,490 control chromosomes in the GnomAD database, including 3,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (579 hom., cov: 32)
  • Exomes 𝑓: 0.062 (2852 hom.)
• Consequence: ANKRD26 NM_014915.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0290
• Publications: 3 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=-0.9).
• BP6: Variant 10-27061127-G-T is Benign according to our data. Variant chr10-27061127-G-T is described in ClinVar as Benign. ClinVar VariationId is 260458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 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.1462+17C>A		intron	N/A	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.1462+17C>A		intron	N/A	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.1462+17C>A		intron	N/A	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.1462+17C>A		intron	N/A	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.1462+17C>A		intron	N/A	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12238 AN: 151932 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0823

GnomAD2 exomes AF: 0.0688 AC: 17135 AN: 249000 AF XY: 0.0688

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.0394

Gnomad ASJ exome AF: 0.0794

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.0660

Gnomad NFE exome AF: 0.0568

Gnomad OTH exome AF: 0.0617

GnomAD4 exome AF: 0.0616 AC: 84777 AN: 1375440 Hom.: 2852 Cov.: 24 AF XY: 0.0626 AC XY: 43150 AN XY: 689174

African (AFR) AF: 0.129 AC: 4071 AN: 31586

American (AMR) AF: 0.0401 AC: 1787 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 2027 AN: 25582

East Asian (EAS) AF: 0.103 AC: 4025 AN: 39170

South Asian (SAS) AF: 0.0880 AC: 7431 AN: 84452

European-Finnish (FIN) AF: 0.0710 AC: 3748 AN: 52824

Middle Eastern (MID) AF: 0.0810 AC: 452 AN: 5582

European-Non Finnish (NFE) AF: 0.0554 AC: 57298 AN: 1034132

Other (OTH) AF: 0.0684 AC: 3938 AN: 57540

GnomAD4 genome AF: 0.0806 AC: 12260 AN: 152050 Hom.: 579 Cov.: 32 AF XY: 0.0795 AC XY: 5905 AN XY: 74294

African (AFR) AF: 0.132 AC: 5475 AN: 41466

American (AMR) AF: 0.0435 AC: 664 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0769 AC: 267 AN: 3470

East Asian (EAS) AF: 0.118 AC: 609 AN: 5168

South Asian (SAS) AF: 0.0838 AC: 404 AN: 4820

European-Finnish (FIN) AF: 0.0640 AC: 676 AN: 10558

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3866 AN: 67982

Other (OTH) AF: 0.0819 AC: 173 AN: 2112

Alfa AF: 0.0441 Hom.: 48

Bravo AF: 0.0813

Asia WGS AF: 0.0920 AC: 320 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Thrombocytopenia 2 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.62
PhyloP100		-0.029
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11015496; hg19: chr10-27350056; COSMIC: COSV65792883;