ENST00000374531.6:c.5+5397T>C

Variant names:

• chr9-109646263-T-C
• rs10816846
• ENST00000374531.6:c.5+5397T>C

Variant summary

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

The ENST00000374531.6(PALM2AKAP2):​c.5+5397T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,196 control chromosomes in the GnomAD database, including 1,375 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 0.12 (1375 hom., cov: 32)
• Consequence: PALM2AKAP2 ENST00000374531.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374531.6. 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_001037293.3		c.5+5397T>C		intron	N/A	NP_001032370.1	Q9Y2D5-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	ENST00000374531.6	TSL:1	c.5+5397T>C		intron	N/A	ENSP00000363656.2	Q9Y2D5-9
	PALM2AKAP2	ENST00000879960.1		c.-2+5397T>C		intron	N/A	ENSP00000550019.1
	PALM2AKAP2	ENST00000674068.1		c.-2+131652T>C		intron	N/A	ENSP00000501308.1	A0A669KBK1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17836 AN: 152078 Hom.: 1376 Cov.: 32

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0939

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.117 AC: 17826 AN: 152196 Hom.: 1375 Cov.: 32 AF XY: 0.121 AC XY: 8998 AN XY: 74408

African (AFR) AF: 0.0341 AC: 1416 AN: 41534

American (AMR) AF: 0.0936 AC: 1432 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3470

East Asian (EAS) AF: 0.0658 AC: 340 AN: 5170

South Asian (SAS) AF: 0.110 AC: 530 AN: 4826

European-Finnish (FIN) AF: 0.237 AC: 2505 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10739 AN: 67990

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.146 Hom.: 939

Bravo AF: 0.103

Asia WGS AF: 0.0820 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-0.38
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: rs10816846; hg19: chr9-112408543;