rs7042004

Positions:

• chr9-109753424-G-A
• chr9-109753424-G-C
• chr9-109753424-G-T

Variant summary

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

The ENST00000374531.6(PALM2AKAP2):​c.6-27064G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,934 control chromosomes in the GnomAD database, including 23,143 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 0.55 (23143 hom., cov: 32)
• Consequence: PALM2AKAP2 ENST00000374531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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 (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM2AKAP2	NM_001037293.3	c.6-27064G>A		intron_variant			NP_001032370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374531.6	c.6-27064G>A		intron_variant		1		ENSP00000363656
PALM2AKAP2	ENST00000674068.1	c.-1-27064G>A		intron_variant				ENSP00000501308

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83155 AN: 151816 Hom.: 23121 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.548 AC: 83240 AN: 151934 Hom.: 23143 Cov.: 32 AF XY: 0.549 AC XY: 40765 AN XY: 74256

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.509

Alfa AF: 0.544 Hom.: 3893

Bravo AF: 0.559

Asia WGS AF: 0.607 AC: 2111 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	1.7
DANN	Benign	0.69

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: rs7042004; hg19: chr9-112515704;