9-110048735-TCCCCCGGAGTCTCCTGGA-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The ENST00000434623.6(PALM2AKAP2):c.64_81del(p.Ser22_Glu27del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 1,538,218 control chromosomes in the GnomAD database, including 2,885 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (199 hom., cov: 30)
  • Exomes 𝑓: 0.058 (2686 hom.)
• Consequence: PALM2AKAP2 ENST00000434623.6 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.910

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 -14 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in ENST00000434623.6.
• BP6: Variant 9-110048735-TCCCCCGGAGTCTCCTGGA-T is Benign according to our data. Variant chr9-110048735-TCCCCCGGAGTCTCCTGGA-T is described in ClinVar as [Benign]. Clinvar id is 252563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALM2AKAP2	NM_007203.5	c.582+32724_582+32741del		intron_variant		ENST00000374530.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.582+32724_582+32741del		intron_variant		2	NM_007203.5

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6381 AN: 151304 Hom.: 200 Cov.: 30

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0791

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0609

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0453

GnomAD3 exomes AF: 0.0395 AC: 5557 AN: 140564 Hom.: 263 AF XY: 0.0426 AC XY: 3333 AN XY: 78148

Gnomad AFR exome AF: 0.00448

Gnomad AMR exome AF: 0.0200

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.0343

Gnomad SAS exome AF: 0.0790

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0487

GnomAD4 exome AF: 0.0580 AC: 80433 AN: 1386798 Hom.: 2686 AF XY: 0.0597 AC XY: 40963 AN XY: 686136

Gnomad4 AFR exome AF: 0.00922

Gnomad4 AMR exome AF: 0.0279

Gnomad4 ASJ exome AF: 0.0719

Gnomad4 EAS exome AF: 0.0527

Gnomad4 SAS exome AF: 0.0982

Gnomad4 FIN exome AF: 0.0228

Gnomad4 NFE exome AF: 0.0584

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.0421 AC: 6371 AN: 151420 Hom.: 199 Cov.: 30 AF XY: 0.0408 AC XY: 3020 AN XY: 74030

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0791

Gnomad4 EAS AF: 0.0510

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.0448

Alfa AF: 0.0221 Hom.: 15

Bravo AF: 0.0405

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Nov 24, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879255366; hg19: chr9-112811015;