Genetic Variant PLEKHA5:c.2119-120A>G (chr12-19319901-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_001256470.2(PLEKHA5):c.2119-120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0867 in 582,802 control chromosomes in the GnomAD database, including 2,543 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 0.093 ( 720 hom., cov: 32)

Exomes 𝑓: 0.085 ( 1823 hom. )

Consequence

PLEKHA5
NM_001256470.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

3 publications found

Variant links:

Genes affected

PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA5 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256470.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLEKHA5	NM_001256470.2	MANE Select	c.2119-120A>G	intron	N/A	NP_001243399.1
PLEKHA5	NM_001385923.1		c.2101-120A>G	intron	N/A	NP_001372852.1
PLEKHA5	NM_001385924.1		c.2119-661A>G	intron	N/A	NP_001372853.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLEKHA5	ENST00000429027.7	TSL:1 MANE Select	c.2119-120A>G	intron	N/A	ENSP00000404296.2
PLEKHA5	ENST00000538714.5	TSL:1	c.2020-661A>G	intron	N/A	ENSP00000439673.1
PLEKHA5	ENST00000299275.10	TSL:1	c.1846-661A>G	intron	N/A	ENSP00000299275.6

Frequencies

GnomAD3 genomes

AF:

0.0927

AC:

14105

AN:

152124

Hom.:

721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.0865

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.0204

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.0405

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0837

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.0845

AC:

36384

AN:

430560

Hom.:

1823

Cov.:

AF XY:

0.0874

AC XY:

20331

AN XY:

232708

show subpopulations

African (AFR)

AF:

0.114

AC:

1122

AN:

9802

American (AMR)

AF:

0.0693

AC:

771

AN:

11132

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

2109

AN:

14596

East Asian (EAS)

AF:

0.0150

AC:

340

AN:

22626

South Asian (SAS)

AF:

0.110

AC:

5257

AN:

47774

European-Finnish (FIN)

AF:

0.0492

AC:

1140

AN:

23172

Middle Eastern (MID)

AF:

0.181

AC:

340

AN:

1880

European-Non Finnish (NFE)

AF:

0.0839

AC:

23217

AN:

276730

Other (OTH)

AF:

0.0914

AC:

2088

AN:

22848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1538

3076

4615

6153

7691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.0928

AC:

14121

AN:

152242

Hom.:

720

Cov.:

AF XY:

0.0912

AC XY:

6788

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.119

AC:

4930

AN:

41568

American (AMR)

AF:

0.0862

AC:

1318

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

541

AN:

3472

East Asian (EAS)

AF:

0.0204

AC:

106

AN:

5188

South Asian (SAS)

AF:

0.101

AC:

488

AN:

4830

European-Finnish (FIN)

AF:

0.0405

AC:

430

AN:

10618

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0837

AC:

5690

AN:

67966

Other (OTH)

AF:

0.115

AC:

242

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

646

1291

1937

2582

3228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0897

Hom.:

417

Bravo

AF:

0.0979

Asia WGS

AF:

0.0580

AC:

203

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.65

PhyloP100

-0.098

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