10-27001161-T-C

Variant names:

• chr10-27001161-T-C
• rs12779247
• ENST00000445828.5:c.561+4462A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000445828.5(ANKRD26):​c.561+4462A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,246 control chromosomes in the GnomAD database, including 794 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.094 (794 hom., cov: 32)
• Consequence: ANKRD26 ENST00000445828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• 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, Ambry Genetics, G2P, 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	XM_017015928.2	c.6085+5756A>G		intron_variant	Intron 34 of 39		XP_016871417.1
ANKRD26	XM_047424821.1	c.6085+5756A>G		intron_variant	Intron 34 of 40		XP_047280777.1
ANKRD26	XM_047424822.1	c.6085+5756A>G		intron_variant	Intron 34 of 35		XP_047280778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000445828.5	c.561+4462A>G		intron_variant	Intron 4 of 5	5		ENSP00000394152.1
ANKRD26	ENST00000674670.1	n.487+5756A>G		intron_variant	Intron 3 of 5			ENSP00000502448.1
ANKRD26	ENST00000675439.1	n.322+5756A>G		intron_variant	Intron 3 of 5			ENSP00000502237.1
ANKRD26	ENST00000675936.1	n.1521+4456A>G		intron_variant	Intron 11 of 12			ENSP00000502093.1

Frequencies

GnomAD3 genomes AF: 0.0935 AC: 14217 AN: 152128 Hom.: 781 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.101

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0937 AC: 14261 AN: 152246 Hom.: 794 Cov.: 32 AF XY: 0.0995 AC XY: 7404 AN XY: 74446

African (AFR) AF: 0.0608 AC: 2527 AN: 41562

American (AMR) AF: 0.118 AC: 1797 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1442 AN: 5156

South Asian (SAS) AF: 0.156 AC: 753 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1331 AN: 10606

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0846 AC: 5754 AN: 68020

Other (OTH) AF: 0.111 AC: 234 AN: 2116

Alfa AF: 0.0862 Hom.: 530

Bravo AF: 0.0900

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.0
DANN	Benign	0.70
PhyloP100		-0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12779247; hg19: chr10-27290090;