dbSNP rs151065500: PALM2AKAP2:p.Pro251Leu (chr9-110136296-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_007203.5(PALM2AKAP2):c.752C>T(p.Pro251Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0101 in 1,614,176 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 5 hom., cov: 32)

Exomes 𝑓: 0.010 ( 117 hom. )

Consequence

PALM2AKAP2
NM_007203.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.62

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004045099).

BP6

Variant 9-110136296-C-T is Benign according to our data. Variant chr9-110136296-C-T is described in ClinVar as Benign. ClinVar VariationId is 777836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00836 (1274/152314) while in subpopulation SAS AF = 0.022 (106/4818). AF 95% confidence interval is 0.0186. There are 5 homozygotes in GnomAd4. There are 659 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALM2AKAP2	NM_007203.5	MANE Select	c.752C>T	p.Pro251Leu	missense	Exon 8 of 11	NP_009134.1	Q9Y2D5-4
PALM2AKAP2	NM_147150.3		c.752C>T	p.Pro251Leu	missense	Exon 8 of 10	NP_671492.1	Q9Y2D5-6
PALM2AKAP2	NM_001198656.1		c.326C>T	p.Pro109Leu	missense	Exon 2 of 5	NP_001185585.1	Q9Y2D5-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.752C>T	p.Pro251Leu	missense	Exon 8 of 11	ENSP00000363654.3	Q9Y2D5-4
PALM2AKAP2	ENST00000434623.6	TSL:1	c.326C>T	p.Pro109Leu	missense	Exon 2 of 5	ENSP00000404782.2	Q9Y2D5-7
PALM2AKAP2	ENST00000374525.5	TSL:1	c.326C>T	p.Pro109Leu	missense	Exon 2 of 4	ENSP00000363649.1	Q9Y2D5-5

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1273

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00507

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00858

AC:

2135

AN:

248898

AF XY:

0.00998

show subpopulations

Gnomad AFR exome

AF:

0.00443

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00374

Gnomad NFE exome

AF:

0.00915

Gnomad OTH exome

AF:

0.00802

GnomAD4 exome

AF:

0.0103

AC:

14994

AN:

1461862

Hom.:

117

Cov.:

AF XY:

0.0108

AC XY:

7843

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00496

AC:

166

AN:

33480

American (AMR)

AF:

0.00546

AC:

244

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0239

AC:

2058

AN:

86246

European-Finnish (FIN)

AF:

0.00425

AC:

227

AN:

53420

Middle Eastern (MID)

AF:

0.0234

AC:

135

AN:

5768

European-Non Finnish (NFE)

AF:

0.0103

AC:

11502

AN:

1111996

Other (OTH)

AF:

0.0101

AC:

609

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1100

2200

3299

4399

5499

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

466

932

1398

1864

2330

<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:

0.00836

AC:

1274

AN:

152314

Hom.:

Cov.:

AF XY:

0.00885

AC XY:

659

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00508

AC:

211

AN:

41572

American (AMR)

AF:

0.0120

AC:

183

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0220

AC:

106

AN:

4818

European-Finnish (FIN)

AF:

0.00367

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0102

AC:

692

AN:

68028

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00895

Hom.:

Bravo

AF:

0.00797

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.00953

AC:

ExAC

AF:

0.00843

AC:

1023

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

PhyloP100

3.6

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

REVEL

Benign

0.028

Sift

Uncertain

0.024

Sift4G

Benign

0.34

Polyphen

0.0040

Vest4

0.085

MVP

0.32

MPC

0.092

ClinPred

0.015

GERP RS

4.4

Varity_R

0.062

gMVP

0.21

Mutation Taster

=96/4

polymorphism

(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