rs2297145

Variant names:

• chr10-27092420-T-C
• rs2297145
• NM_014915.3:c.624A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-27092420-T-C
• chr10-27092420-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014915.3(ANKRD26):​c.624A>G​(p.Val208Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,607,082 control chromosomes in the GnomAD database, including 38,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4875 hom., cov: 32)
  • Exomes 𝑓: 0.20 (33778 hom.)
• Consequence: ANKRD26 NM_014915.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.38
• Publications: 28 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 10-27092420-T-C is Benign according to our data. Variant chr10-27092420-T-C is described in ClinVar as Benign. ClinVar VariationId is 260473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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.624A>G	p.Val208Val	synonymous	Exon 4 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.624A>G	p.Val208Val	synonymous	Exon 4 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.624A>G	p.Val208Val	synonymous	Exon 4 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.624A>G	p.Val208Val	synonymous	Exon 4 of 34	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.624A>G	p.Val208Val	synonymous	Exon 4 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35778 AN: 151946 Hom.: 4853 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.242 AC: 59829 AN: 247536 AF XY: 0.244

Gnomad AFR exome AF: 0.312

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.195 AC: 284013 AN: 1455018 Hom.: 33778 Cov.: 31 AF XY: 0.199 AC XY: 144413 AN XY: 724138

African (AFR) AF: 0.305 AC: 10143 AN: 33308

American (AMR) AF: 0.194 AC: 8628 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5605 AN: 26076

East Asian (EAS) AF: 0.578 AC: 22881 AN: 39596

South Asian (SAS) AF: 0.364 AC: 31298 AN: 86014

European-Finnish (FIN) AF: 0.250 AC: 13244 AN: 52984

Middle Eastern (MID) AF: 0.217 AC: 1168 AN: 5378

European-Non Finnish (NFE) AF: 0.161 AC: 178014 AN: 1106996

Other (OTH) AF: 0.217 AC: 13032 AN: 60126

GnomAD4 genome AF: 0.236 AC: 35847 AN: 152064 Hom.: 4875 Cov.: 32 AF XY: 0.245 AC XY: 18188 AN XY: 74342

African (AFR) AF: 0.310 AC: 12866 AN: 41446

American (AMR) AF: 0.197 AC: 3013 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2855 AN: 5154

South Asian (SAS) AF: 0.385 AC: 1857 AN: 4824

European-Finnish (FIN) AF: 0.257 AC: 2716 AN: 10570

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11125 AN: 67998

Other (OTH) AF: 0.233 AC: 493 AN: 2112

Alfa AF: 0.187 Hom.: 9723

Bravo AF: 0.232

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-1.0
CADD	Benign	0.20
DANN	Benign	0.52
PhyloP100		-1.4
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: rs2297145; hg19: chr10-27381349; COSMIC: COSV108209677; COSMIC: COSV108209677;