rs9696126

Positions:

• chr9-110147856-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.2996-8463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,142 control chromosomes in the GnomAD database, including 1,755 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 0.14 (1755 hom., cov: 32)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM2AKAP2	NM_007203.5	c.2996-8463C>T		intron_variant		ENST00000374530.8	NP_009134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.2996-8463C>T		intron_variant		2	NM_007203.5	ENSP00000363654

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20980 AN: 152024 Hom.: 1754 Cov.: 32

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.138 AC: 20975 AN: 152142 Hom.: 1755 Cov.: 32 AF XY: 0.136 AC XY: 10126 AN XY: 74380

Gnomad4 AFR AF: 0.0530

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0985

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.132

Alfa AF: 0.173 Hom.: 1257

Bravo AF: 0.138

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.90

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: rs9696126; hg19: chr9-112910136;