9-109759255-T-C

Position:

• chr9-109759255-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM2AKAP2	NM_001037293.3	c.6-21233T>C		intron_variant			NP_001032370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374531.6	c.6-21233T>C		intron_variant		1		ENSP00000363656
PALM2AKAP2	ENST00000674068.1	c.-1-21233T>C		intron_variant				ENSP00000501308

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

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.615

Alfa AF: 0.587 Hom.: 34739

Bravo AF: 0.673

Asia WGS AF: 0.753 AC: 2620 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.48

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: rs2025878; hg19: chr9-112521535;