chr10-27028849-T-C

Variant names:

• chr10-27028849-T-C
• rs72807627
• NM_014915.3:c.3972+3A>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.3972+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 1,607,462 control chromosomes in the GnomAD database, including 8,403 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (790 hom., cov: 32)
  • Exomes 𝑓: 0.092 (7613 hom.)
• Consequence: ANKRD26 NM_014915.3 splice_region, intron
• Scores: Splicing: ADA: 0.0002748
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.405
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 10-27028849-T-C is Benign according to our data. Variant chr10-27028849-T-C is described in ClinVar as Benign. ClinVar VariationId is 260468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD26	NM_014915.3	MANE Select	c.3972+3A>G		splice_region intron	N/A	NP_055730.2
	ANKRD26	NM_001256053.2		c.3969+3A>G		splice_region intron	N/A	NP_001242982.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD26	ENST00000376087.5	TSL:5 MANE Select	c.3972+3A>G		splice_region intron	N/A	ENSP00000365255.4
	ANKRD26	ENST00000436985.7	TSL:1	c.3969+3A>G		splice_region intron	N/A	ENSP00000405112.3
	ANKRD26	ENST00000675116.1		n.*295+3A>G		splice_region intron	N/A	ENSP00000501975.1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14123 AN: 152046 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0998

GnomAD2 exomes AF: 0.113 AC: 28190 AN: 248670 AF XY: 0.114

Gnomad AFR exome AF: 0.0597

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.291

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.0848

Gnomad OTH exome AF: 0.0969

GnomAD4 exome AF: 0.0921 AC: 134084 AN: 1455298 Hom.: 7613 Cov.: 31 AF XY: 0.0934 AC XY: 67616 AN XY: 724218

African (AFR) AF: 0.0582 AC: 1941 AN: 33368

American (AMR) AF: 0.111 AC: 4973 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2693 AN: 26058

East Asian (EAS) AF: 0.270 AC: 10644 AN: 39440

South Asian (SAS) AF: 0.142 AC: 12179 AN: 85906

European-Finnish (FIN) AF: 0.111 AC: 5923 AN: 53348

Middle Eastern (MID) AF: 0.0970 AC: 557 AN: 5742

European-Non Finnish (NFE) AF: 0.0804 AC: 88965 AN: 1106626

Other (OTH) AF: 0.103 AC: 6209 AN: 60140

GnomAD4 genome AF: 0.0931 AC: 14159 AN: 152164 Hom.: 790 Cov.: 32 AF XY: 0.0990 AC XY: 7365 AN XY: 74402

African (AFR) AF: 0.0588 AC: 2442 AN: 41532

American (AMR) AF: 0.117 AC: 1792 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3468

East Asian (EAS) AF: 0.280 AC: 1449 AN: 5172

South Asian (SAS) AF: 0.156 AC: 753 AN: 4820

European-Finnish (FIN) AF: 0.125 AC: 1321 AN: 10582

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

European-Non Finnish (NFE) AF: 0.0845 AC: 5747 AN: 67990

Other (OTH) AF: 0.110 AC: 232 AN: 2116

Alfa AF: 0.0818 Hom.: 302

Bravo AF: 0.0894

Asia WGS AF: 0.240 AC: 834 AN: 3474

ClinVar

ClinVar submissions as Germline

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	-0.54
CADD	Benign	12
DANN	Benign	0.55
PhyloP100		0.41
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.060		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: rs72807627; hg19: chr10-27317778; COSMIC: COSV65775812;