9-109923769-G-C

Variant names:

• chr9-109923769-G-C
• rs759984551
• NM_007203.5:c.292G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_007203.5(PALM2AKAP2):​c.292G>C​(p.Glu98Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E98K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PALM2AKAP2 NM_007203.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.12
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
PALM2AKAP2	NM_007203.5	c.292G>C	p.Glu98Gln	missense_variant	Exon 4 of 11	ENST00000374530.8	NP_009134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.292G>C	p.Glu98Gln	missense_variant	Exon 4 of 11	2	NM_007203.5	ENSP00000363654.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;.;.;.;.
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D
M_CAP	Benign	0.0081	T
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.;.;.
PhyloP100		9.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N;N
REVEL	Uncertain	0.37
Sift	Benign	0.22	T;T;T;D;D;D;.
Sift4G	Benign	0.11	T;T;T;T;T;T;T
Polyphen		1.0	D;.;.;.;.;.;.
Vest4		0.55
MutPred		0.42		Gain of glycosylation at S101 (P = 0.1168);.;.;.;.;.;.;
MVP		0.72
MPC		0.82, 0.21
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.17
gMVP		0.64
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs759984551; hg19: chr9-112686049;