9-109925074-C-G

Variant names:

• chr9-109925074-C-G
• rs150674445
• NM_007203.5:c.386C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007203.5(PALM2AKAP2):​c.386C>G​(p.Thr129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. T129M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PALM2AKAP2 NM_007203.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13178834).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	NM_007203.5	MANE Select	c.386C>G	p.Thr129Arg	missense	Exon 5 of 11	NP_009134.1	Q9Y2D5-4
	PALM2AKAP2	NM_147150.3		c.386C>G	p.Thr129Arg	missense	Exon 5 of 10	NP_671492.1	Q9Y2D5-6
	PALM2AKAP2	NM_053016.6		c.386C>G	p.Thr129Arg	missense	Exon 5 of 7	NP_443749.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.386C>G	p.Thr129Arg	missense	Exon 5 of 11	ENSP00000363654.3	Q9Y2D5-4
	PALM2AKAP2	ENST00000314527.9	TSL:1	c.386C>G	p.Thr129Arg	missense	Exon 5 of 7	ENSP00000323805.4	Q9Y2D5-8
	PALM2AKAP2	ENST00000374531.6	TSL:1	c.392C>G	p.Thr131Arg	missense	Exon 6 of 7	ENSP00000363656.2	Q9Y2D5-9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461848 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.042
Sift	Benign	0.24	T
Sift4G	Benign	0.12	T
Polyphen		0.025	B
Vest4		0.23
MutPred		0.40		Loss of phosphorylation at T131 (P = 0.0404)
MVP		0.27
MPC		0.33
ClinPred		0.33	T
GERP RS		4.5
Varity_R		0.097
gMVP		0.20
Mutation Taster		=91/9	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

Other links and lift over

dbSNP: rs150674445; hg19: chr9-112687354;