10-97578255-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001346793.2(ANKRD2):​c.205C>G​(p.Arg69Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,604,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R69L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ANKRD2
NM_001346793.2 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43
Variant links:
Genes affected
ANKRD2 (HGNC:495): (ankyrin repeat domain 2) This gene encodes a protein that belongs to the muscle ankyrin repeat protein (MARP) family. A similar gene in rodents is a component of a muscle stress response pathway and plays a role in the stretch-response associated with slow muscle function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ANKRD2NM_001346793.2 linkc.205C>G p.Arg69Gly missense_variant Exon 3 of 9 ENST00000370655.6 NP_001333722.1 A0A0A0MRN9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ANKRD2ENST00000370655.6 linkc.205C>G p.Arg69Gly missense_variant Exon 3 of 9 1 NM_001346793.2 ENSP00000359689.1 A0A0A0MRN9
ANKRD2ENST00000307518.9 linkc.286C>G p.Arg96Gly missense_variant Exon 3 of 9 1 ENSP00000306163.5 Q9GZV1-1
ANKRD2ENST00000298808.9 linkc.286C>G p.Arg96Gly missense_variant Exon 3 of 8 1 ENSP00000298808.5 Q9GZV1-2
ANKRD2ENST00000455090.1 linkc.205C>G p.Arg69Gly missense_variant Exon 3 of 8 1 ENSP00000403114.1 Q5T457

Frequencies

GnomAD3 genomes
AF:
0.0000199
AC:
3
AN:
150986
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000443
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000809
AC:
2
AN:
247180
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134680
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000234
AC:
34
AN:
1453482
Hom.:
0
Cov.:
35
AF XY:
0.0000207
AC XY:
15
AN XY:
723104
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000307
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000199
AC:
3
AN:
150986
Hom.:
0
Cov.:
31
AF XY:
0.0000407
AC XY:
3
AN XY:
73658
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000443
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.286C>G (p.R96G) alteration is located in exon 3 (coding exon 3) of the ANKRD2 gene. This alteration results from a C to G substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a glycine (G). 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
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;.;.;T
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.88
D;D;D;D
M_CAP
Benign
0.079
D
MetaRNN
Uncertain
0.44
T;T;T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Uncertain
2.4
M;M;.;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.4
N;N;N;N
REVEL
Uncertain
0.30
Sift
Benign
0.067
T;T;T;T
Sift4G
Uncertain
0.0040
D;D;D;D
Polyphen
1.0
D;D;.;.
Vest4
0.51
MutPred
0.42
Loss of stability (P = 0.0472);Loss of stability (P = 0.0472);.;.;
MVP
0.84
MPC
0.89
ClinPred
0.97
D
GERP RS
5.3
Varity_R
0.28
gMVP
0.85

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: rs369179658; hg19: chr10-99338012; API