10-27100466-G-C

Variant names:

• chr10-27100466-G-C
• rs41299222
• NM_014915.3:c.-140C>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.-140C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,297,204 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (267 hom., cov: 34)
  • Exomes 𝑓: 0.047 (1417 hom.)
• Consequence: ANKRD26 NM_014915.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.58
• Publications: 14 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 (BayesDel_noAF=-0.56).
• BP6: Variant 10-27100466-G-C is Benign according to our data. Variant chr10-27100466-G-C is described in ClinVar as Benign. ClinVar VariationId is 260453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0809 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.-140C>G		5_prime_UTR	Exon 1 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.-140C>G		5_prime_UTR	Exon 1 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.-140C>G		5_prime_UTR	Exon 1 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.-140C>G		5_prime_UTR	Exon 1 of 34	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.-140C>G		5_prime_UTR	Exon 1 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8524 AN: 152208 Hom.: 265 Cov.: 34

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0431

GnomAD4 exome AF: 0.0468 AC: 53584 AN: 1144878 Hom.: 1417 Cov.: 15 AF XY: 0.0463 AC XY: 26376 AN XY: 569224

African (AFR) AF: 0.0845 AC: 2177 AN: 25762

American (AMR) AF: 0.0220 AC: 500 AN: 22698

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 1350 AN: 19232

East Asian (EAS) AF: 0.00173 AC: 62 AN: 35814

South Asian (SAS) AF: 0.0301 AC: 1963 AN: 65140

European-Finnish (FIN) AF: 0.0549 AC: 1730 AN: 31524

Middle Eastern (MID) AF: 0.0443 AC: 151 AN: 3406

European-Non Finnish (NFE) AF: 0.0486 AC: 43332 AN: 892268

Other (OTH) AF: 0.0473 AC: 2319 AN: 49034

GnomAD4 genome AF: 0.0561 AC: 8540 AN: 152326 Hom.: 267 Cov.: 34 AF XY: 0.0549 AC XY: 4089 AN XY: 74484

African (AFR) AF: 0.0832 AC: 3460 AN: 41584

American (AMR) AF: 0.0331 AC: 507 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0706 AC: 245 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5186

South Asian (SAS) AF: 0.0269 AC: 130 AN: 4832

European-Finnish (FIN) AF: 0.0518 AC: 550 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0516 AC: 3510 AN: 68020

Other (OTH) AF: 0.0426 AC: 90 AN: 2112

Alfa AF: 0.0614 Hom.: 40

Bravo AF: 0.0564

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Thrombocytopenia 2 (4)
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.2
DANN	Benign	0.81
PhyloP100		-1.6
PromoterAI		0.54	Over-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=168/132	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs41299222; hg19: chr10-27389395;