rs2274741

Variant names:

• chr10-27014676-A-T
• rs2274741
• NM_014915.3:c.4542T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-27014676-A-T
• chr10-27014676-A-G

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.4542T>A​(p.Phe1514Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,612,226 control chromosomes in the GnomAD database, including 31,615 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3638 hom., cov: 32)
  • Exomes 𝑓: 0.17 (27977 hom.)
• Consequence: ANKRD26 NM_014915.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.718
• Publications: 21 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 (MetaRNN=1.1472558E-4).
• BP6: Variant 10-27014676-A-T is Benign according to our data. Variant chr10-27014676-A-T is described in ClinVar as Benign. ClinVar VariationId is 260470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 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.4542T>A	p.Phe1514Leu	missense	Exon 31 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.4539T>A	p.Phe1513Leu	missense	Exon 31 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.4542T>A	p.Phe1514Leu	missense	Exon 31 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.4539T>A	p.Phe1513Leu	missense	Exon 31 of 34	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.5628T>A	p.Phe1876Leu	missense	Exon 32 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30341 AN: 151996 Hom.: 3620 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.194

GnomAD2 exomes AF: 0.221 AC: 54924 AN: 248202 AF XY: 0.225

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.182

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.552

Gnomad FIN exome AF: 0.240

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.173 AC: 252402 AN: 1460112 Hom.: 27977 Cov.: 32 AF XY: 0.178 AC XY: 128954 AN XY: 726344

African (AFR) AF: 0.222 AC: 7429 AN: 33420

American (AMR) AF: 0.182 AC: 8114 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 5068 AN: 26104

East Asian (EAS) AF: 0.577 AC: 22838 AN: 39588

South Asian (SAS) AF: 0.344 AC: 29601 AN: 86168

European-Finnish (FIN) AF: 0.236 AC: 12581 AN: 53374

Middle Eastern (MID) AF: 0.191 AC: 1044 AN: 5470

European-Non Finnish (NFE) AF: 0.139 AC: 153963 AN: 1111056

Other (OTH) AF: 0.195 AC: 11764 AN: 60298

GnomAD4 genome AF: 0.200 AC: 30408 AN: 152114 Hom.: 3638 Cov.: 32 AF XY: 0.210 AC XY: 15621 AN XY: 74356

African (AFR) AF: 0.226 AC: 9369 AN: 41506

American (AMR) AF: 0.179 AC: 2727 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 648 AN: 3470

East Asian (EAS) AF: 0.557 AC: 2885 AN: 5182

South Asian (SAS) AF: 0.368 AC: 1775 AN: 4820

European-Finnish (FIN) AF: 0.243 AC: 2567 AN: 10546

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9806 AN: 68004

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.164 Hom.: 1940

Bravo AF: 0.193

TwinsUK AF: 0.149 AC: 554

ALSPAC AF: 0.139 AC: 534

ESP6500AA AF: 0.233 AC: 841

ESP6500EA AF: 0.145 AC: 1181

ExAC AF: 0.222 AC: 26755

Asia WGS AF: 0.457 AC: 1585 AN: 3474

EpiCase AF: 0.148

EpiControl AF: 0.151

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
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.31
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.031	T
MetaRNN	Benign	0.00011	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.72
PrimateAI	Benign	0.41	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.055
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.034
MPC		0.052
ClinPred		0.0047	T
GERP RS		1.3
PromoterAI		-0.0051	Neutral
Varity_R		0.041
gMVP		0.013
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: rs2274741; hg19: chr10-27303605; COSMIC: COSV65774511;