chr10-27067142-T-C

Variant names:

• chr10-27067142-T-C
• rs115864032
• NM_014915.3:c.1207+15A>G

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.1207+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 1,610,764 control chromosomes in the GnomAD database, including 1,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (91 hom., cov: 31)
  • Exomes 𝑓: 0.035 (945 hom.)
• Consequence: ANKRD26 NM_014915.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.178
• 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=-0.88).
• BP6: Variant 10-27067142-T-C is Benign according to our data. Variant chr10-27067142-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260455.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 = 0.0334 (5080/152278) while in subpopulation NFE AF = 0.0389 (2644/68024). AF 95% confidence interval is 0.0376. There are 91 homozygotes in GnomAd4. There are 2449 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5080 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.1207+15A>G		intron	N/A	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.1207+15A>G		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.1207+15A>G		intron	N/A	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.1207+15A>G		intron	N/A	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.1207+15A>G		intron	N/A	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5079 AN: 152160 Hom.: 91 Cov.: 31

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0574

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0315 AC: 7838 AN: 249018 AF XY: 0.0317

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.0142

Gnomad ASJ exome AF: 0.0575

Gnomad EAS exome AF: 0.00389

Gnomad FIN exome AF: 0.0416

Gnomad NFE exome AF: 0.0383

Gnomad OTH exome AF: 0.0332

GnomAD4 exome AF: 0.0349 AC: 50924 AN: 1458486 Hom.: 945 Cov.: 31 AF XY: 0.0349 AC XY: 25293 AN XY: 725708

African (AFR) AF: 0.0300 AC: 1003 AN: 33416

American (AMR) AF: 0.0152 AC: 681 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 1507 AN: 26106

East Asian (EAS) AF: 0.00229 AC: 91 AN: 39664

South Asian (SAS) AF: 0.0281 AC: 2418 AN: 86190

European-Finnish (FIN) AF: 0.0417 AC: 2201 AN: 52830

Middle Eastern (MID) AF: 0.0347 AC: 185 AN: 5338

European-Non Finnish (NFE) AF: 0.0367 AC: 40705 AN: 1109980

Other (OTH) AF: 0.0354 AC: 2133 AN: 60250

GnomAD4 genome AF: 0.0334 AC: 5080 AN: 152278 Hom.: 91 Cov.: 31 AF XY: 0.0329 AC XY: 2449 AN XY: 74476

African (AFR) AF: 0.0291 AC: 1208 AN: 41558

American (AMR) AF: 0.0245 AC: 375 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 199 AN: 3464

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4820

European-Finnish (FIN) AF: 0.0395 AC: 419 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2644 AN: 68024

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0396 Hom.: 25

Bravo AF: 0.0319

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		0.18
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: rs115864032; hg19: chr10-27356071;