10-27014582-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014915.3(ANKRD26):​c.4636G>A​(p.Asp1546Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,453,506 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1546H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ANKRD26
NM_014915.3 missense

Scores

3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.35
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16853431).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD26NM_014915.3 linkc.4636G>A p.Asp1546Asn missense_variant Exon 31 of 34 ENST00000376087.5 NP_055730.2 Q9UPS8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD26ENST00000376087.5 linkc.4636G>A p.Asp1546Asn missense_variant Exon 31 of 34 5 NM_014915.3 ENSP00000365255.4 Q9UPS8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1453506
Hom.:
0
Cov.:
31
AF XY:
0.00000415
AC XY:
3
AN XY:
723172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
20
DANN
Uncertain
0.99
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-0.90
T
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Benign
0.14
Sift
Benign
0.069
T;T
Sift4G
Uncertain
0.041
D;D
Vest4
0.19
MVP
0.30
MPC
0.064
ClinPred
0.84
D
GERP RS
2.0
Varity_R
0.21
gMVP
0.073

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs753924410; hg19: chr10-27303511; API