rs16914575

Variant names:

• chr9-109879209-G-A
• rs16914575
• NM_007203.5:c.127-1342G>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.127-1342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0995 in 152,148 control chromosomes in the GnomAD database, including 1,259 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 0.099 (1259 hom., cov: 33)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM2AKAP2	NM_007203.5	c.127-1342G>A		intron_variant	Intron 2 of 10	ENST00000374530.8	NP_009134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM2AKAP2	ENST00000374530.8	c.127-1342G>A		intron_variant	Intron 2 of 10	2	NM_007203.5	ENSP00000363654.3

Frequencies

GnomAD3 genomes AF: 0.0995 AC: 15128 AN: 152030 Hom.: 1262 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0398

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0995 AC: 15136 AN: 152148 Hom.: 1259 Cov.: 33 AF XY: 0.101 AC XY: 7529 AN XY: 74398

African (AFR) AF: 0.223 AC: 9236 AN: 41460

American (AMR) AF: 0.0605 AC: 926 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.113 AC: 589 AN: 5190

South Asian (SAS) AF: 0.192 AC: 923 AN: 4812

European-Finnish (FIN) AF: 0.0492 AC: 521 AN: 10600

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0398 AC: 2708 AN: 68000

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0551 Hom.: 682

Bravo AF: 0.102

Asia WGS AF: 0.149 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.47
PhyloP100		-0.24
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: rs16914575; hg19: chr9-112641489;