9-109749146-A-G

Variant names:

• chr9-109749146-A-G
• rs3902539
• ENST00000374531.6:c.6-31342A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374531.6(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 ENST00000374531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 2 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374531.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	NM_001037293.3		c.6-31342A>G		intron	N/A	NP_001032370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374531.6	TSL:1	c.6-31342A>G		intron	N/A	ENSP00000363656.2
	PALM2AKAP2	ENST00000674068.1		c.-1-31342A>G		intron	N/A	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

African (AFR) AF: 0.961 AC: 39921 AN: 41538

American (AMR) AF: 0.867 AC: 13241 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2924 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4622 AN: 5168

South Asian (SAS) AF: 0.877 AC: 4217 AN: 4810

European-Finnish (FIN) AF: 0.813 AC: 8616 AN: 10602

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53508 AN: 67992

Other (OTH) AF: 0.841 AC: 1777 AN: 2112

Alfa AF: 0.826 Hom.: 9090

Bravo AF: 0.862

Asia WGS AF: 0.885 AC: 3081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.16
DANN	Benign	0.58
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs3902539; hg19: chr9-112511426;