rs138423863

Variant names:

• chr10-27053356-CTCT-C
• rs138423863
• NM_014915.3:c.1596_1598delAGA

Your query was ambiguous. Multiple possible variants found:

• chr10-27053356-CTCT-C
• chr10-27053356-CTCT-CTCTTCT

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_014915.3(ANKRD26):​c.1596_1598delAGA​(p.Glu533del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,611,050 control chromosomes in the GnomAD database, including 1,828 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (150 hom., cov: 32)
  • Exomes 𝑓: 0.017 (1678 hom.)
• Consequence: ANKRD26 NM_014915.3 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.70
• Publications: 5 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 -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_014915.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-27053356-CTCT-C is Benign according to our data. Variant chr10-27053356-CTCT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 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.1596_1598delAGA	p.Glu533del	disruptive_inframe_deletion	Exon 16 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.1596_1598delAGA	p.Glu533del	disruptive_inframe_deletion	Exon 16 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.1596_1598delAGA	p.Glu533del	disruptive_inframe_deletion	Exon 16 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.1596_1598delAGA	p.Glu533del	disruptive_inframe_deletion	Exon 16 of 34	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.1596_1598delAGA	p.Glu533del	disruptive_inframe_deletion	Exon 16 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2748 AN: 152014 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.0362 AC: 8988 AN: 248570 AF XY: 0.0393

Gnomad AFR exome AF: 0.00757

Gnomad AMR exome AF: 0.0293

Gnomad ASJ exome AF: 0.00954

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.0570

Gnomad NFE exome AF: 0.00350

Gnomad OTH exome AF: 0.0256

GnomAD4 exome AF: 0.0171 AC: 24910 AN: 1458918 Hom.: 1678 AF XY: 0.0198 AC XY: 14393 AN XY: 725792

African (AFR) AF: 0.00754 AC: 252 AN: 33426

American (AMR) AF: 0.0272 AC: 1218 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00992 AC: 259 AN: 26096

East Asian (EAS) AF: 0.204 AC: 8059 AN: 39484

South Asian (SAS) AF: 0.111 AC: 9566 AN: 85812

European-Finnish (FIN) AF: 0.0524 AC: 2757 AN: 52584

Middle Eastern (MID) AF: 0.00892 AC: 51 AN: 5718

European-Non Finnish (NFE) AF: 0.00141 AC: 1564 AN: 1110828

Other (OTH) AF: 0.0196 AC: 1184 AN: 60266

GnomAD4 genome AF: 0.0181 AC: 2749 AN: 152132 Hom.: 150 Cov.: 32 AF XY: 0.0235 AC XY: 1750 AN XY: 74360

African (AFR) AF: 0.00744 AC: 309 AN: 41550

American (AMR) AF: 0.0139 AC: 212 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.156 AC: 805 AN: 5166

South Asian (SAS) AF: 0.127 AC: 611 AN: 4816

European-Finnish (FIN) AF: 0.0548 AC: 578 AN: 10554

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 67982

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00903 Hom.: 7

Bravo AF: 0.0131

Asia WGS AF: 0.121 AC: 417 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
Mutation Taster		=92/8	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: rs138423863; hg19: chr10-27342285; COSMIC: COSV65776540;