rs10816846

Positions:

• chr9-109646263-T-C

Variant summary

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

The ENST00000374531.6(PALM2AKAP2):​c.5+5397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,196 control chromosomes in the GnomAD database, including 1,375 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 0.12 (1375 hom., cov: 32)
• Consequence: PALM2AKAP2 ENST00000374531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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 (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM2AKAP2	NM_001037293.3	c.5+5397T>C		intron_variant			NP_001032370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374531.6	c.5+5397T>C		intron_variant		1		ENSP00000363656
PALM2AKAP2	ENST00000674068.1	c.-2+131652T>C		intron_variant				ENSP00000501308

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17836 AN: 152078 Hom.: 1376 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.117 AC: 17826 AN: 152196 Hom.: 1375 Cov.: 32 AF XY: 0.121 AC XY: 8998 AN XY: 74408

Gnomad4 AFR AF: 0.0341

Gnomad4 AMR AF: 0.0936

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.122

Alfa AF: 0.146 Hom.: 853

Bravo AF: 0.103

Asia WGS AF: 0.0820 AC: 283 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	1.2
DANN	Benign	0.70

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: rs10816846; hg19: chr9-112408543;