rs41279942

Variant names:

• chr10-27092468-C-T
• rs41279942
• NM_014915.3:c.576G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_014915.3(ANKRD26):​c.576G>A​(p.Gln192Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,613,338 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (21 hom., cov: 32)
  • Exomes 𝑓: 0.016 (246 hom.)
• Consequence: ANKRD26 NM_014915.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.919
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-27092468-C-T is Benign according to our data. Variant chr10-27092468-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.919 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0131 (1993/152232) while in subpopulation NFE AF = 0.0222 (1508/68000). AF 95% confidence interval is 0.0212. There are 21 homozygotes in GnomAd4. There are 969 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1993 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD26	NM_014915.3	MANE Select	c.576G>A	p.Gln192Gln	synonymous	Exon 4 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.576G>A	p.Gln192Gln	synonymous	Exon 4 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.576G>A	p.Gln192Gln	synonymous	Exon 4 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.576G>A	p.Gln192Gln	synonymous	Exon 4 of 34	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.576G>A	p.Gln192Gln	synonymous	Exon 4 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1994 AN: 152114 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00307

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.0169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.0132 AC: 3293 AN: 249020 AF XY: 0.0138

Gnomad AFR exome AF: 0.00343

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.0167

Gnomad NFE exome AF: 0.0202

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0163 AC: 23770 AN: 1461106 Hom.: 246 Cov.: 31 AF XY: 0.0164 AC XY: 11886 AN XY: 726862

African (AFR) AF: 0.00239 AC: 80 AN: 33476

American (AMR) AF: 0.00371 AC: 166 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 325 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.00881 AC: 760 AN: 86240

European-Finnish (FIN) AF: 0.0172 AC: 916 AN: 53174

Middle Eastern (MID) AF: 0.00521 AC: 30 AN: 5762

European-Non Finnish (NFE) AF: 0.0187 AC: 20755 AN: 1111600

Other (OTH) AF: 0.0122 AC: 737 AN: 60374

GnomAD4 genome AF: 0.0131 AC: 1993 AN: 152232 Hom.: 21 Cov.: 32 AF XY: 0.0130 AC XY: 969 AN XY: 74432

African (AFR) AF: 0.00306 AC: 127 AN: 41548

American (AMR) AF: 0.00419 AC: 64 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4832

European-Finnish (FIN) AF: 0.0169 AC: 179 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0222 AC: 1508 AN: 68000

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.0196 Hom.: 50

Bravo AF: 0.0111

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0167

EpiControl AF: 0.0163

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.86
CADD	Benign	1.8
DANN	Benign	0.37
PhyloP100		-0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41279942; hg19: chr10-27381397;