rs41299210

Variant names:

• chr10-27035066-C-T
• rs41299210
• NM_014915.3:c.3384G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_014915.3(ANKRD26):​c.3384G>A​(p.Lys1128Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,613,328 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (18 hom., cov: 32)
  • Exomes 𝑓: 0.023 (499 hom.)
• Consequence: ANKRD26 NM_014915.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:7
• Conservation: PhyloP100: 0.465
• 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, 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 10-27035066-C-T is Benign according to our data. Variant chr10-27035066-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.465 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0147 (2231/152280) while in subpopulation NFE AF = 0.022 (1496/67996). AF 95% confidence interval is 0.0211. There are 18 homozygotes in GnomAd4. There are 1035 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2231 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.3384G>A	p.Lys1128Lys	synonymous	Exon 24 of 34	NP_055730.2	Q9UPS8-1
	ANKRD26	NM_001256053.2		c.3381G>A	p.Lys1127Lys	synonymous	Exon 24 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.3384G>A	p.Lys1128Lys	synonymous	Exon 24 of 34	ENSP00000365255.4	Q9UPS8-1
	ANKRD26	ENST00000436985.7	TSL:1	c.3381G>A	p.Lys1127Lys	synonymous	Exon 24 of 34	ENSP00000405112.3	E7ESJ3
	ANKRD26	ENST00000968143.1		c.4470G>A	p.Lys1490Lys	synonymous	Exon 25 of 35	ENSP00000638202.1

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2234 AN: 152162 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.0175 AC: 4350 AN: 248588 AF XY: 0.0181

Gnomad AFR exome AF: 0.00530

Gnomad AMR exome AF: 0.00759

Gnomad ASJ exome AF: 0.0377

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.0131

Gnomad NFE exome AF: 0.0218

Gnomad OTH exome AF: 0.0209

GnomAD4 exome AF: 0.0233 AC: 34081 AN: 1461048 Hom.: 499 Cov.: 32 AF XY: 0.0233 AC XY: 16903 AN XY: 726800

African (AFR) AF: 0.00485 AC: 162 AN: 33404

American (AMR) AF: 0.00775 AC: 346 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 954 AN: 26090

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39678

South Asian (SAS) AF: 0.0244 AC: 2102 AN: 86088

European-Finnish (FIN) AF: 0.0132 AC: 701 AN: 53298

Middle Eastern (MID) AF: 0.0226 AC: 130 AN: 5760

European-Non Finnish (NFE) AF: 0.0255 AC: 28395 AN: 1111768

Other (OTH) AF: 0.0213 AC: 1283 AN: 60344

GnomAD4 genome AF: 0.0147 AC: 2231 AN: 152280 Hom.: 18 Cov.: 32 AF XY: 0.0139 AC XY: 1035 AN XY: 74454

African (AFR) AF: 0.00486 AC: 202 AN: 41578

American (AMR) AF: 0.0110 AC: 169 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4828

European-Finnish (FIN) AF: 0.0105 AC: 111 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0220 AC: 1496 AN: 67996

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0201 Hom.: 28

Bravo AF: 0.0141

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.0221

EpiControl AF: 0.0198

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.4
DANN	Benign	0.56
PhyloP100		0.47
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: rs41299210; hg19: chr10-27323995;