rs149655759

Variant names:

• chr10-27060339-A-G
• rs149655759
• NM_014915.3:c.1564+6T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014915.3(ANKRD26):​c.1564+6T>C variant causes a splice 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.03147
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.601
• 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=-0.67).
• BP6: Variant 10-27060339-A-G is Benign according to our data. Variant chr10-27060339-A-G is described in ClinVar as Benign. ClinVar VariationId is 260459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2573 AD gene.

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.1564+6T>C		splice_region intron	N/A	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.1564+6T>C		splice_region 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.1564+6T>C		splice_region intron	N/A	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.1564+6T>C		splice_region intron	N/A	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.1564+6T>C		splice_region intron	N/A	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2573 AN: 152148 Hom.: 32 Cov.: 32

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

GnomAD2 exomes AF: 0.0186 AC: 4636 AN: 249110 AF XY: 0.0187

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 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.: 30 AF XY: 0.0219 AC XY: 15746 AN XY: 719056

African (AFR) AF: 0.00285 AC: 94 AN: 33014

American (AMR) AF: 0.00703 AC: 314 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0286 AC: 745 AN: 26010

East Asian (EAS) AF: 0.00119 AC: 47 AN: 39482

South Asian (SAS) AF: 0.0142 AC: 1216 AN: 85718

European-Finnish (FIN) AF: 0.0282 AC: 1508 AN: 53396

Middle Eastern (MID) AF: 0.00806 AC: 46 AN: 5706

European-Non Finnish (NFE) AF: 0.0242 AC: 26511 AN: 1095294

Other (OTH) AF: 0.0208 AC: 1244 AN: 59818

GnomAD4 genome AF: 0.0169 AC: 2573 AN: 152266 Hom.: 32 Cov.: 32 AF XY: 0.0163 AC XY: 1210 AN XY: 74444

African (AFR) AF: 0.00397 AC: 165 AN: 41560

American (AMR) AF: 0.0117 AC: 179 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5186

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4816

European-Finnish (FIN) AF: 0.0258 AC: 273 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0256 AC: 1739 AN: 68020

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.0234 Hom.: 23

Bravo AF: 0.0147

Asia WGS AF: 0.0160 AC: 56 AN: 3474

EpiCase AF: 0.0248

EpiControl AF: 0.0218

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.5
DANN	Benign	0.69
PhyloP100		0.60
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs149655759; hg19: chr10-27349268;