Genetic Variant PALM2AKAP2:c.582+107A>G (chr9-110016146-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007203.5(PALM2AKAP2):c.582+107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,089,860 control chromosomes in the GnomAD database, including 23,222 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 0.20 ( 3193 hom., cov: 31)

Exomes 𝑓: 0.20 ( 20029 hom. )

Consequence

PALM2AKAP2
NM_007203.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Publications

3 publications found

Variant links:

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]

PALM2AKAP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM2AKAP2	NM_007203.5	MANE Select	c.582+107A>G		intron	N/A	NP_009134.1
	PALM2AKAP2	NM_147150.3		c.582+107A>G		intron	N/A	NP_671492.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.582+107A>G	intron	N/A	ENSP00000363654.3
PALM2AKAP2	ENST00000302798.7	TSL:2	c.582+107A>G	intron	N/A	ENSP00000305861.7
PALM2AKAP2	ENST00000413420.5	TSL:2	c.1278+107A>G	intron	N/A	ENSP00000397839.1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31028

AN:

151902

Hom.:

3193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.250

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.168

GnomAD4 exome

AF:

0.202

AC:

189754

AN:

937840

Hom.:

20029

AF XY:

0.202

AC XY:

96257

AN XY:

477652

show subpopulations

African (AFR)

AF:

0.198

AC:

4477

AN:

22644

American (AMR)

AF:

0.147

AC:

4999

AN:

33954

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

4292

AN:

21448

East Asian (EAS)

AF:

0.281

AC:

9345

AN:

33268

South Asian (SAS)

AF:

0.183

AC:

12660

AN:

69114

European-Finnish (FIN)

AF:

0.250

AC:

11721

AN:

46826

Middle Eastern (MID)

AF:

0.137

AC:

607

AN:

4426

European-Non Finnish (NFE)

AF:

0.201

AC:

133470

AN:

664066

Other (OTH)

AF:

0.194

AC:

8183

AN:

42094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

7460

14920

22381

29841

37301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3764

7528

11292

15056

18820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.204

AC:

31056

AN:

152020

Hom.:

3193

Cov.:

AF XY:

0.204

AC XY:

15175

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.202

AC:

8358

AN:

41462

American (AMR)

AF:

0.167

AC:

2550

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

658

AN:

3466

East Asian (EAS)

AF:

0.275

AC:

1418

AN:

5164

South Asian (SAS)

AF:

0.190

AC:

915

AN:

4816

European-Finnish (FIN)

AF:

0.250

AC:

2635

AN:

10560

Middle Eastern (MID)

AF:

0.164

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.205

AC:

13961

AN:

67960

Other (OTH)

AF:

0.168

AC:

356

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1269

2538

3807

5076

6345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.198

Hom.:

5343

Bravo

AF:

0.201

Asia WGS

AF:

0.199

AC:

692

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.5

(source)

DANN

Benign

0.51

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over