chr12-56244951-C-T

Variant summary

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

The NM_173595.4(ANKRD52):​c.2531G>A​(p.Gly844Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ANKRD52
NM_173595.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58
Variant links:
Genes affected
ANKRD52 (HGNC:26614): (ankyrin repeat domain 52)

Genome browser will be placed here

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=0.07526991).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD52NM_173595.4 linkc.2531G>A p.Gly844Glu missense_variant Exon 23 of 28 ENST00000267116.8 NP_775866.2 Q8NB46B3KWN0
ANKRD52XM_017019183.2 linkc.2528G>A p.Gly843Glu missense_variant Exon 22 of 27 XP_016874672.1
ANKRD52XM_011538197.3 linkc.2348G>A p.Gly783Glu missense_variant Exon 22 of 27 XP_011536499.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD52ENST00000267116.8 linkc.2531G>A p.Gly844Glu missense_variant Exon 23 of 28 1 NM_173595.4 ENSP00000267116.7 Q8NB46
ANKRD52ENST00000548241.1 linkn.-224G>A upstream_gene_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249204
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135204
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461702
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727136
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2531G>A (p.G844E) alteration is located in exon 23 (coding exon 23) of the ANKRD52 gene. This alteration results from a G to A substitution at nucleotide position 2531, causing the glycine (G) at amino acid position 844 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
20
DANN
Benign
0.59
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.075
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.23
N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
1.8
N
REVEL
Benign
0.071
Sift
Benign
1.0
T
Sift4G
Benign
0.99
T
Polyphen
0.0
B
Vest4
0.29
MutPred
0.34
Gain of catalytic residue at A848 (P = 0.083);
MVP
0.21
MPC
1.0
ClinPred
0.28
T
GERP RS
3.6
Varity_R
0.053
gMVP
0.62

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: rs1413557900; hg19: chr12-56638735; API