chr9-110136407-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007203.5(PALM2AKAP2):āc.863A>Gā(p.Asp288Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 32)
Exomes š: 0.000011 ( 0 hom. )
Consequence
PALM2AKAP2
NM_007203.5 missense
NM_007203.5 missense
Scores
6
9
2
Clinical Significance
Conservation
PhyloP100: 7.95
Genes affected
PALM2AKAP2 (HGNC:33529): (PALM2 and AKAP2 fusion) This gene belongs to the paralemmin downstream gene (PDG) family defined in PMID:22855693. Paralemmin downstream genes may have evolved contiguously with the paralemmin genes and are associated with other paralemmin paralogs in humans and several other taxa. The gene encodes three distinct protein isoforms, the PALM2 isoform, the AKAP2 isoform and the PALM2-AKAP2 isoform. The biological significance of the PALM2-AKAP2 isoforms is yet unknown. Earlier, PALM2 and AKAP2 were annotated as separate genes and PALM2-AKAP2 was annotated as a readthrough gene. [provided by RefSeq, May 2019]
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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 | UniProt |
---|---|---|---|---|---|---|---|
PALM2AKAP2 | NM_007203.5 | c.863A>G | p.Asp288Gly | missense_variant | 8/11 | ENST00000374530.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PALM2AKAP2 | ENST00000374530.8 | c.863A>G | p.Asp288Gly | missense_variant | 8/11 | 2 | NM_007203.5 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152170Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249036Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134806
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727248
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74338
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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 08, 2023 | The c.863A>G (p.D288G) alteration is located in exon 8 (coding exon 8) of the PALM2-AKAP2 gene. This alteration results from a A to G substitution at nucleotide position 863, causing the aspartic acid (D) at amino acid position 288 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0, 1.0
.;.;D;D;D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at