rs995294

chr9-109977064-C-T

Variant summary

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

The NM_007203.5(PALM2AKAP2):c.497-38890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,870 control chromosomes in the GnomAD database, including 9,761 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 0.33 (9761 hom., cov: 31)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALM2AKAP2	NM_007203.5	c.497-38890C>T		intron_variant		ENST00000374530.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.497-38890C>T		intron_variant		2	NM_007203.5
PALM2AKAP2	ENST00000302798.7	c.497-38890C>T		intron_variant		2
PALM2AKAP2	ENST00000413420.5	c.1192+33683C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50635 AN: 151752 Hom.: 9761 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.333 AC: 50643 AN: 151870 Hom.: 9761 Cov.: 31 AF XY: 0.329 AC XY: 24388 AN XY: 74210

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.353

Alfa AF: 0.424 Hom.: 17663

Bravo AF: 0.329

Asia WGS AF: 0.160 AC: 557 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.95
Dann	Benign	0.27

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: rs995294; hg19: chr9-112739344;