rs1327796

Positions:

• chr9-109764009-C-G
• chr9-109764009-C-T

Variant summary

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

The ENST00000374531.6(PALM2AKAP2):​c.6-16479C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,054 control chromosomes in the GnomAD database, including 3,075 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 0.20 (3075 hom., cov: 32)
• Consequence: PALM2AKAP2 ENST00000374531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107987013	NR_171891.1	n.445+1404G>C		intron_variant, non_coding_transcript_variant
PALM2AKAP2	NM_001037293.3	c.6-16479C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM2AKAP2	ENST00000374531.6	c.6-16479C>G		intron_variant		1
	ENST00000449258.3	n.486+1404G>C		intron_variant, non_coding_transcript_variant		3
PALM2AKAP2	ENST00000674068.1	c.-1-16479C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29922 AN: 151936 Hom.: 3070 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.197 AC: 29952 AN: 152054 Hom.: 3075 Cov.: 32 AF XY: 0.199 AC XY: 14802 AN XY: 74330

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.180

Alfa AF: 0.182 Hom.: 1417

Bravo AF: 0.197

Asia WGS AF: 0.254 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.60

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: rs1327796; hg19: chr9-112526289; COSMIC: COSV65759149;