rs1969944

Variant names:

• chr9-110141579-G-A
• rs1969944
• NM_007203.5:c.2995+3040G>A

Variant summary

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

The NM_007203.5(PALM2AKAP2):​c.2995+3040G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,184 control chromosomes in the GnomAD database, including 51,179 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 0.82 (51179 hom., cov: 31)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 11 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM2AKAP2	NM_007203.5	c.2995+3040G>A		intron_variant	Intron 8 of 10	ENST00000374530.8	NP_009134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.2995+3040G>A		intron_variant	Intron 8 of 10	2	NM_007203.5	ENSP00000363654.3

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124483 AN: 152066 Hom.: 51125 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.821

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

GnomAD4 genome AF: 0.819 AC: 124596 AN: 152184 Hom.: 51179 Cov.: 31 AF XY: 0.817 AC XY: 60750 AN XY: 74390

African (AFR) AF: 0.876 AC: 36396 AN: 41528

American (AMR) AF: 0.843 AC: 12892 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2325 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4039 AN: 5174

South Asian (SAS) AF: 0.665 AC: 3206 AN: 4822

European-Finnish (FIN) AF: 0.835 AC: 8846 AN: 10588

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54406 AN: 67996

Other (OTH) AF: 0.824 AC: 1737 AN: 2108

Alfa AF: 0.796 Hom.: 37258

Bravo AF: 0.825

Asia WGS AF: 0.762 AC: 2648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.36
DANN	Benign	0.74
PhyloP100		0.034
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: rs1969944; hg19: chr9-112903859;