9-109749146-A-G

Position:

• chr9-109749146-A-G

Variant summary

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

The NM_001037293.3(PALM2AKAP2):​c.6-31342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 152,176 control chromosomes in the GnomAD database, including 55,820 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 0.85 (55820 hom., cov: 31)
• Consequence: PALM2AKAP2 NM_001037293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM2AKAP2	NM_001037293.3	c.6-31342A>G		intron_variant			NP_001032370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374531.6	c.6-31342A>G		intron_variant		1		ENSP00000363656.2
PALM2AKAP2	ENST00000674068.1	c.-1-31342A>G		intron_variant				ENSP00000501308.1

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129717 AN: 152058 Hom.: 55752 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.853 AC: 129846 AN: 152176 Hom.: 55820 Cov.: 31 AF XY: 0.854 AC XY: 63561 AN XY: 74402

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.841

Alfa AF: 0.822 Hom.: 8740

Bravo AF: 0.862

Asia WGS AF: 0.885 AC: 3081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.16
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs3902539; hg19: chr9-112511426;