ENST00000374531.6:c.5+28812G>A

Variant names:

• chr9-109669678-G-A
• rs10816852
• ENST00000374531.6:c.5+28812G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374531.6(PALM2AKAP2):​c.5+28812G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 151,682 control chromosomes in the GnomAD database, including 773 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 0.095 (773 hom., cov: 32)
• Consequence: PALM2AKAP2 ENST00000374531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374531.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	NM_001037293.3		c.5+28812G>A		intron	N/A	NP_001032370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374531.6	TSL:1	c.5+28812G>A		intron	N/A	ENSP00000363656.2
	PALM2AKAP2	ENST00000674068.1		c.-1-110810G>A		intron	N/A	ENSP00000501308.1

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14393 AN: 151562 Hom.: 774 Cov.: 32

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.0816

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0871

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.0825

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

GnomAD4 genome AF: 0.0950 AC: 14405 AN: 151682 Hom.: 773 Cov.: 32 AF XY: 0.100 AC XY: 7442 AN XY: 74134

African (AFR) AF: 0.0849 AC: 3515 AN: 41410

American (AMR) AF: 0.0948 AC: 1444 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0551 AC: 191 AN: 3466

East Asian (EAS) AF: 0.244 AC: 1260 AN: 5164

South Asian (SAS) AF: 0.0818 AC: 394 AN: 4814

European-Finnish (FIN) AF: 0.164 AC: 1707 AN: 10412

Middle Eastern (MID) AF: 0.0759 AC: 22 AN: 290

European-Non Finnish (NFE) AF: 0.0829 AC: 5624 AN: 67874

Other (OTH) AF: 0.0817 AC: 172 AN: 2106

Alfa AF: 0.0853 Hom.: 336

Bravo AF: 0.0880

Asia WGS AF: 0.152 AC: 527 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.47
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10816852; hg19: chr9-112431958;