10-27030329-T-C

Variant names:

• chr10-27030329-T-C
• rs11015463
• NM_014915.3:c.3808-973A>G

Variant summary

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

The NM_014915.3(ANKRD26):​c.3808-973A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 936,668 control chromosomes in the GnomAD database, including 274,763 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 0.79 (48259 hom., cov: 32)
  • Exomes 𝑓: 0.76 (226504 hom.)
• Consequence: ANKRD26 NM_014915.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• 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, 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.3808-973A>G		intron_variant	Intron 25 of 33	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.3808-973A>G		intron_variant	Intron 25 of 33	5	NM_014915.3	ENSP00000365255.4
ANKRD26	ENST00000436985.7	c.3805-973A>G		intron_variant	Intron 25 of 33	1		ENSP00000405112.3
ANKRD26	ENST00000675116.1	n.*130+64A>G		intron_variant	Intron 6 of 14			ENSP00000501975.1
ANKRD26	ENST00000675936.1	n.223-973A>G		intron_variant	Intron 2 of 12			ENSP00000502093.1

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120715 AN: 152018 Hom.: 48238 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.759 AC: 595606 AN: 784532 Hom.: 226504 AF XY: 0.759 AC XY: 275945 AN XY: 363510

African (AFR) AF: 0.812 AC: 11993 AN: 14768

American (AMR) AF: 0.687 AC: 632 AN: 920

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 3898 AN: 4850

East Asian (EAS) AF: 0.993 AC: 3369 AN: 3394

South Asian (SAS) AF: 0.846 AC: 13058 AN: 15434

European-Finnish (FIN) AF: 0.898 AC: 239 AN: 266

Middle Eastern (MID) AF: 0.784 AC: 1188 AN: 1516

European-Non Finnish (NFE) AF: 0.754 AC: 541212 AN: 717756

Other (OTH) AF: 0.781 AC: 20017 AN: 25628

GnomAD4 genome AF: 0.794 AC: 120782 AN: 152136 Hom.: 48259 Cov.: 32 AF XY: 0.804 AC XY: 59814 AN XY: 74402

African (AFR) AF: 0.816 AC: 33858 AN: 41486

American (AMR) AF: 0.725 AC: 11082 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2777 AN: 3468

East Asian (EAS) AF: 0.989 AC: 5125 AN: 5182

South Asian (SAS) AF: 0.862 AC: 4149 AN: 4816

European-Finnish (FIN) AF: 0.872 AC: 9242 AN: 10604

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.766 AC: 52051 AN: 67992

Other (OTH) AF: 0.786 AC: 1654 AN: 2104

Alfa AF: 0.773 Hom.: 132202

Bravo AF: 0.782

Asia WGS AF: 0.909 AC: 3159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.8
DANN	Benign	0.50
PhyloP100		0.22
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: rs11015463; hg19: chr10-27319258;