rs260214

Positions:

• chr9-110047214-C-G
• chr9-110047214-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.582+31175C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,108 control chromosomes in the GnomAD database, including 40,988 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 0.73 (40988 hom., cov: 32)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM2AKAP2	NM_007203.5	c.582+31175C>G		intron_variant		ENST00000374530.8	NP_009134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.582+31175C>G		intron_variant		2	NM_007203.5	ENSP00000363654
PALM2AKAP2	ENST00000302798.7	c.582+31175C>G		intron_variant		2		ENSP00000305861
PALM2AKAP2	ENST00000413420.5	c.1278+31175C>G		intron_variant		2		ENSP00000397839

Frequencies

GnomAD3 genomes AF: 0.730 AC: 111028 AN: 151992 Hom.: 40937 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.731 AC: 111142 AN: 152108 Hom.: 40988 Cov.: 32 AF XY: 0.727 AC XY: 54067 AN XY: 74344

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.731

Alfa AF: 0.716 Hom.: 4585

Bravo AF: 0.744

Asia WGS AF: 0.630 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.58

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: rs260214; hg19: chr9-112809494;