Genetic Variant PALM2AKAP2:p.Glu40Glu (chr9-110048819-A-G) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001198656.1(PALM2AKAP2):c.120A>G(p.Glu40Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,528,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PALM2AKAP2
NM_001198656.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.193

Publications

0 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-110048819-A-G is Benign according to our data. Variant chr9-110048819-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 734613.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.193 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198656.1. 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.582+32780A>G		intron	N/A	NP_009134.1	Q9Y2D5-4
PALM2AKAP2	NM_001198656.1		c.120A>G	p.Glu40Glu	synonymous	Exon 1 of 5	NP_001185585.1	Q9Y2D5-7
PALM2AKAP2	NM_001004065.4		c.120A>G	p.Glu40Glu	synonymous	Exon 1 of 4	NP_001004065.2	Q9Y2D5-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PALM2AKAP2	ENST00000434623.6	TSL:1	c.120A>G	p.Glu40Glu	synonymous	Exon 1 of 5	ENSP00000404782.2	Q9Y2D5-7
PALM2AKAP2	ENST00000374525.5	TSL:1	c.120A>G	p.Glu40Glu	synonymous	Exon 1 of 4	ENSP00000363649.1	Q9Y2D5-5
PALM2AKAP2	ENST00000374530.8	TSL:2 MANE Select	c.582+32780A>G		intron	N/A	ENSP00000363654.3	Q9Y2D5-4

Frequencies

GnomAD3 genomes

AF:

0.000102

AC:

AN:

147744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000278

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.000491

GnomAD2 exomes

AF:

0.0000157

AC:

AN:

127690

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000164

Gnomad AMR exome

AF:

0.0000413

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1380488

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

681224

show subpopulations

African (AFR)

AF:

0.000351

AC:

AN:

31364

American (AMR)

AF:

0.000113

AC:

AN:

35526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25028

East Asian (EAS)

AF:

0.00

AC:

AN:

35500

South Asian (SAS)

AF:

0.00

AC:

AN:

78974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5196

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077274

Other (OTH)

AF:

0.00

AC:

AN:

57666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000102

AC:

AN:

147744

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

72026

show subpopulations

African (AFR)

AF:

0.000278

AC:

AN:

39530

American (AMR)

AF:

0.000135

AC:

AN:

14868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4764

South Asian (SAS)

AF:

0.00

AC:

AN:

4588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67144

Other (OTH)

AF:

0.000491

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

0.19

PromoterAI

-0.040

Neutral

(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