rs41299222

Variant names:

• chr10-27100466-G-A
• rs41299222
• NM_014915.3:c.-140C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-27100466-G-A
• chr10-27100466-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014915.3(ANKRD26):​c.-140C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,145,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: ANKRD26 NM_014915.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD26	NM_014915.3	c.-140C>T		5_prime_UTR_variant	Exon 1 of 34	ENST00000376087.5	NP_055730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD26	ENST00000376087.5	c.-140C>T		5_prime_UTR_variant	Exon 1 of 34	5	NM_014915.3	ENSP00000365255.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000262 AC: 3 AN: 1145442 Hom.: 0 Cov.: 15 AF XY: 0.00000351 AC XY: 2 AN XY: 569478

African (AFR) AF: 0.00 AC: 0 AN: 25790

American (AMR) AF: 0.00 AC: 0 AN: 22700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19240

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35814

South Asian (SAS) AF: 0.00 AC: 0 AN: 65148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3406

European-Non Finnish (NFE) AF: 0.00000224 AC: 2 AN: 892760

Other (OTH) AF: 0.00 AC: 0 AN: 49056

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.0
DANN	Benign	0.87
PhyloP100		-1.6
PromoterAI		0.40	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=168/132	polymorphism

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: rs41299222; hg19: chr10-27389395;