9-109780523-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007203.5(PALM2AKAP2):​c.35A>G​(p.Gln12Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00034 in 1,613,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

PALM2AKAP2
NM_007203.5 missense

Scores

1
11
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.35

Publications

1 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19983825).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PALM2AKAP2NM_007203.5 linkc.35A>G p.Gln12Arg missense_variant Exon 1 of 11 ENST00000374530.8 NP_009134.1 Q9Y2D5-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PALM2AKAP2ENST00000374530.8 linkc.35A>G p.Gln12Arg missense_variant Exon 1 of 11 2 NM_007203.5 ENSP00000363654.3

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000470
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000207
AC:
52
AN:
251448
AF XY:
0.000184
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000440
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000352
AC:
514
AN:
1461320
Hom.:
0
Cov.:
31
AF XY:
0.000334
AC XY:
243
AN XY:
726964
show subpopulations
African (AFR)
AF:
0.000120
AC:
4
AN:
33468
American (AMR)
AF:
0.0000224
AC:
1
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86214
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5346
European-Non Finnish (NFE)
AF:
0.000451
AC:
501
AN:
1111976
Other (OTH)
AF:
0.000116
AC:
7
AN:
60336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
31
62
94
125
156
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152226
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74356
show subpopulations
African (AFR)
AF:
0.0000482
AC:
2
AN:
41462
American (AMR)
AF:
0.0000654
AC:
1
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000470
AC:
32
AN:
68032
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000343
Hom.:
0
Bravo
AF:
0.000200
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000222
AC:
27
EpiCase
AF:
0.000273
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.35A>G (p.Q12R) alteration is located in exon 1 (coding exon 1) of the PALM2-AKAP2 gene. This alteration results from a A to G substitution at nucleotide position 35, causing the glutamine (Q) at amino acid position 12 to be replaced by an arginine (R). 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
0.32
BayesDel_addAF
Benign
-0.034
T
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
T;.;.;.;.;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.88
D;D;D;D;D;D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.20
T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Uncertain
2.0
M;.;.;.;.;.
PhyloP100
6.4
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.0
D;D;D;N;D;N
REVEL
Benign
0.24
Sift
Pathogenic
0.0
D;D;D;D;D;.
Sift4G
Uncertain
0.0090
D;D;D;D;D;D
Polyphen
0.15
B;.;.;.;.;.
Vest4
0.83
MVP
0.50
MPC
0.37, 0.092
ClinPred
0.26
T
GERP RS
5.2
PromoterAI
0.087
Neutral
Varity_R
0.55
gMVP
0.33
Mutation Taster
=78/22
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs145552511; hg19: chr9-112542803; API