rs527666933

Variant names:

• chr10-27100510-C-A
• rs527666933
• NM_014915.3:c.-184G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-27100510-C-A
• chr10-27100510-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014915.3(ANKRD26):​c.-184G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 885,920 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 34)
  • Exomes 𝑓: 0.0048 (23 hom.)
• Consequence: ANKRD26 NM_014915.3 upstream_gene
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.80
• Publications: 0 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=-0.5).
• BP6: Variant 10-27100510-C-A is Benign according to our data. Variant chr10-27100510-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 434211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00493 (751/152376) while in subpopulation NFE AF = 0.00563 (383/68034). AF 95% confidence interval is 0.00516. There are 3 homozygotes in GnomAd4. There are 449 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High AC in GnomAd4 at 751 AD gene.

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.-184G>T		upstream_gene	N/A	NP_055730.2
	ANKRD26	NM_001256053.2		c.-184G>T		upstream_gene	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.-184G>T		upstream_gene	N/A	ENSP00000365255.4
	ANKRD26	ENST00000436985.7	TSL:1	c.-184G>T		upstream_gene	N/A	ENSP00000405112.3
	ANKRD26	ENST00000675187.1		n.-184G>T		upstream_gene	N/A	ENSP00000502611.1

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 751 AN: 152258 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00563

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00475 AC: 3485 AN: 733544 Hom.: 23 Cov.: 10 AF XY: 0.00465 AC XY: 1736 AN XY: 373312

African (AFR) AF: 0.000917 AC: 16 AN: 17442

American (AMR) AF: 0.00104 AC: 20 AN: 19272

Ashkenazi Jewish (ASJ) AF: 0.0000646 AC: 1 AN: 15488

East Asian (EAS) AF: 0.00 AC: 0 AN: 32588

South Asian (SAS) AF: 0.00 AC: 0 AN: 51866

European-Finnish (FIN) AF: 0.0247 AC: 730 AN: 29574

Middle Eastern (MID) AF: 0.000395 AC: 1 AN: 2532

European-Non Finnish (NFE) AF: 0.00488 AC: 2581 AN: 529384

Other (OTH) AF: 0.00384 AC: 136 AN: 35398

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152376 Hom.: 3 Cov.: 34 AF XY: 0.00603 AC XY: 449 AN XY: 74512

African (AFR) AF: 0.000769 AC: 32 AN: 41598

American (AMR) AF: 0.00183 AC: 28 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0272 AC: 289 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00563 AC: 383 AN: 68034

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00455 Hom.: 0

Bravo AF: 0.00298

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	2.0
DANN	Benign	0.83
PhyloP100		-1.8
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs527666933; hg19: chr10-27389439;