rs995294

Variant names:

• chr9-109977064-C-T
• rs995294
• NM_007203.5:c.497-38890C>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.497-38890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,870 control chromosomes in the GnomAD database, including 9,761 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 0.33 (9761 hom., cov: 31)
• Consequence: PALM2AKAP2 NM_007203.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 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.497-38890C>T		intron	N/A	NP_009134.1	Q9Y2D5-4
	PALM2AKAP2	NM_147150.3		c.497-38890C>T		intron	N/A	NP_671492.1	Q9Y2D5-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.497-38890C>T		intron	N/A	ENSP00000363654.3	Q9Y2D5-4
	PALM2AKAP2	ENST00000302798.7	TSL:2	c.497-38890C>T		intron	N/A	ENSP00000305861.7	Q9Y2D5-6
	PALM2AKAP2	ENST00000879960.1		c.497-38890C>T		intron	N/A	ENSP00000550019.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50635 AN: 151752 Hom.: 9761 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.333 AC: 50643 AN: 151870 Hom.: 9761 Cov.: 31 AF XY: 0.329 AC XY: 24388 AN XY: 74210

African (AFR) AF: 0.155 AC: 6442 AN: 41440

American (AMR) AF: 0.404 AC: 6162 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3470

East Asian (EAS) AF: 0.109 AC: 565 AN: 5168

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4808

European-Finnish (FIN) AF: 0.366 AC: 3842 AN: 10494

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29962 AN: 67906

Other (OTH) AF: 0.353 AC: 747 AN: 2114

Alfa AF: 0.418 Hom.: 24531

Bravo AF: 0.329

Asia WGS AF: 0.160 AC: 557 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.27
PhyloP100		-0.23
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: rs995294; hg19: chr9-112739344;