9-109637985-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000674068.1(PALM2AKAP2):c.-2+123374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,012 control chromosomes in the GnomAD database, including 33,042 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (33042 hom., cov: 31)
• Consequence: PALM2AKAP2 ENST00000674068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM2AKAP2	ENST00000674068.1	c.-2+123374A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97709 AN: 151894 Hom.: 32994 Cov.: 31

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.643 AC: 97810 AN: 152012 Hom.: 33042 Cov.: 31 AF XY: 0.643 AC XY: 47785 AN XY: 74306

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.614

Alfa AF: 0.616 Hom.: 4205

Bravo AF: 0.636

Asia WGS AF: 0.567 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1923433; hg19: chr9-112400265;