chr1-117887766-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017686.4(GDAP2):c.962G>A(p.Arg321His) variant causes a missense change. The variant allele was found at a frequency of 0.0000202 in 1,535,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
GDAP2
NM_017686.4 missense
NM_017686.4 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 7.02
Genes affected
GDAP2 (HGNC:18010): (ganglioside induced differentiation associated protein 2) Predicted to act upstream of or within response to retinoic acid. Located in lysosomal membrane. Implicated in autosomal recessive spinocerebellar ataxia 27. [provided by Alliance of Genome Resources, Apr 2022]
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GDAP2 | NM_017686.4 | c.962G>A | p.Arg321His | missense_variant | 9/14 | ENST00000369443.10 | NP_060156.1 | |
GDAP2 | NM_001135589.3 | c.962G>A | p.Arg321His | missense_variant | 9/13 | NP_001129061.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GDAP2 | ENST00000369443.10 | c.962G>A | p.Arg321His | missense_variant | 9/14 | 2 | NM_017686.4 | ENSP00000358451 | P1 | |
GDAP2 | ENST00000369442.3 | c.962G>A | p.Arg321His | missense_variant | 9/13 | 1 | ENSP00000358450 | |||
GDAP2 | ENST00000464026.1 | n.240G>A | non_coding_transcript_exon_variant | 3/5 | 2 | |||||
GDAP2 | ENST00000491626.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151828Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
4
AN:
151828
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000480 AC: 12AN: 249992Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135188
GnomAD3 exomes
AF:
AC:
12
AN:
249992
Hom.:
AF XY:
AC XY:
6
AN XY:
135188
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000195 AC: 27AN: 1384116Hom.: 0 Cov.: 23 AF XY: 0.0000188 AC XY: 13AN XY: 693046
GnomAD4 exome
AF:
AC:
27
AN:
1384116
Hom.:
Cov.:
23
AF XY:
AC XY:
13
AN XY:
693046
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151828Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74106
GnomAD4 genome
AF:
AC:
4
AN:
151828
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74106
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
6
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.962G>A (p.R321H) alteration is located in exon 9 (coding exon 8) of the GDAP2 gene. This alteration results from a G to A substitution at nucleotide position 962, causing the arginine (R) at amino acid position 321 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0077);Loss of MoRF binding (P = 0.0077);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at