rs9696126

Variant names:

• chr9-110147856-C-T
• rs9696126
• NM_007203.5:c.2996-8463C>T

Variant summary

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

The NM_007203.5(PALM2AKAP2):​c.2996-8463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,142 control chromosomes in the GnomAD database, including 1,755 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 0.14 (1755 hom., cov: 32)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	NM_007203.5	MANE Select	c.2996-8463C>T		intron	N/A	NP_009134.1	Q9Y2D5-4
	PALM2AKAP2	NM_147150.3		c.2996-8463C>T		intron	N/A	NP_671492.1	Q9Y2D5-6
	PALM2AKAP2	NM_001198656.1		c.2570-8463C>T		intron	N/A	NP_001185585.1	Q9Y2D5-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.2996-8463C>T		intron	N/A	ENSP00000363654.3	Q9Y2D5-4
	PALM2AKAP2	ENST00000434623.6	TSL:1	c.2570-8463C>T		intron	N/A	ENSP00000404782.2	Q9Y2D5-7
	PALM2AKAP2	ENST00000374525.5	TSL:1	c.2570-8463C>T		intron	N/A	ENSP00000363649.1	Q9Y2D5-5

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20980 AN: 152024 Hom.: 1754 Cov.: 32

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0996

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.138 AC: 20975 AN: 152142 Hom.: 1755 Cov.: 32 AF XY: 0.136 AC XY: 10126 AN XY: 74380

African (AFR) AF: 0.0530 AC: 2199 AN: 41500

American (AMR) AF: 0.171 AC: 2620 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3472

East Asian (EAS) AF: 0.0985 AC: 511 AN: 5188

South Asian (SAS) AF: 0.150 AC: 722 AN: 4816

European-Finnish (FIN) AF: 0.149 AC: 1581 AN: 10576

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12434 AN: 67992

Other (OTH) AF: 0.132 AC: 278 AN: 2110

Alfa AF: 0.172 Hom.: 1702

Bravo AF: 0.138

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.90
PhyloP100		0.26
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: rs9696126; hg19: chr9-112910136;