rs2025875

Positions:

• chr9-109834631-G-A
• chr9-109834631-G-C

Variant summary

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

The NM_007203.5(PALM2AKAP2):​c.46-32860G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,168 control chromosomes in the GnomAD database, including 52,489 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 0.83 (52489 hom., cov: 31)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALM2AKAP2	NM_007203.5	c.46-32860G>A		intron_variant		ENST00000374530.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.46-32860G>A		intron_variant		2	NM_007203.5

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125720 AN: 152050 Hom.: 52424 Cov.: 31

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.827 AC: 125846 AN: 152168 Hom.: 52489 Cov.: 31 AF XY: 0.825 AC XY: 61370 AN XY: 74354

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.809

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.813

Alfa AF: 0.781 Hom.: 53287

Bravo AF: 0.836

Asia WGS AF: 0.828 AC: 2877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.57

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: rs2025875; hg19: chr9-112596911; COSMIC: COSV57115946;