9-109759255-T-C

Variant names:

• chr9-109759255-T-C
• rs2025878
• ENST00000374531.6:c.6-21233T>C

Variant summary

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

The ENST00000374531.6(PALM2AKAP2):​c.6-21233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,920 control chromosomes in the GnomAD database, including 34,561 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 0.67 (34561 hom., cov: 32)
• Consequence: PALM2AKAP2 ENST00000374531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 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.6-21233T>C		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.6-21233T>C		intron	N/A	ENSP00000363656.2
	PALM2AKAP2	ENST00000674068.1		c.-1-21233T>C		intron	N/A	ENSP00000501308.1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101110 AN: 151804 Hom.: 34527 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.666 AC: 101208 AN: 151920 Hom.: 34561 Cov.: 32 AF XY: 0.670 AC XY: 49732 AN XY: 74238

African (AFR) AF: 0.812 AC: 33692 AN: 41486

American (AMR) AF: 0.667 AC: 10154 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1818 AN: 3466

East Asian (EAS) AF: 0.726 AC: 3755 AN: 5174

South Asian (SAS) AF: 0.765 AC: 3689 AN: 4824

European-Finnish (FIN) AF: 0.626 AC: 6598 AN: 10544

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39425 AN: 67876

Other (OTH) AF: 0.615 AC: 1298 AN: 2112

Alfa AF: 0.604 Hom.: 88560

Bravo AF: 0.673

Asia WGS AF: 0.753 AC: 2620 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.34
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: rs2025878; hg19: chr9-112521535;