rs1407392

chr9-109626179-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+111568A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,990 control chromosomes in the GnomAD database, including 14,411 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 0.43 (14411 hom., cov: 32)
• Consequence: PALM2AKAP2 ENST00000674068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 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+111568A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65110 AN: 151872 Hom.: 14392 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.429 AC: 65170 AN: 151990 Hom.: 14411 Cov.: 32 AF XY: 0.422 AC XY: 31311 AN XY: 74270

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.429

Alfa AF: 0.438 Hom.: 2118

Bravo AF: 0.418

Asia WGS AF: 0.343 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.1
Dann	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1407392; hg19: chr9-112388459;