Genetic Variant PLEKHB2:p.Pro67Leu (chr2-131126693-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is . The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001100623.2(PLEKHB2):c.200C>T(p.Pro67Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000969 in 1,445,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

PLEKHB2
NM_001100623.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.89

Publications

0 publications found

Variant links:

Genes affected

PLEKHB2 (HGNC:19236): (pleckstrin homology domain containing B2) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity. Predicted to be involved in regulation of cell differentiation. Predicted to be located in recycling endosome membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHB2 links:

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new If you want to explore the variant's impact on the transcript NM_001100623.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.141).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100623.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLEKHB2	NM_001100623.2	MANE Select	c.200C>T	p.Pro67Leu	missense	Exon 4 of 8	NP_001094093.1	Q96CS7-1
PLEKHB2	NM_001267062.2		c.200C>T	p.Pro67Leu	missense	Exon 4 of 9	NP_001253991.1	A0A0A0MSE9
PLEKHB2	NM_001267063.2		c.200C>T	p.Pro67Leu	missense	Exon 4 of 9	NP_001253992.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLEKHB2	ENST00000693505.1	MANE Select	c.200C>T	p.Pro67Leu	missense	Exon 4 of 8	ENSP00000510611.1	Q96CS7-1
PLEKHB2	ENST00000409279.1	TSL:2	c.200C>T	p.Pro67Leu	missense	Exon 4 of 8	ENSP00000386666.1	Q96CS7-1
PLEKHB2	ENST00000234115.10	TSL:1	c.200C>T	p.Pro67Leu	missense	Exon 4 of 8	ENSP00000234115.6	Q96CS7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000969

AC:

AN:

1445314

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

720176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33148

American (AMR)

AF:

0.00

AC:

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.00

AC:

AN:

85886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.0000128

AC:

AN:

1097004

Other (OTH)

AF:

0.00

AC:

AN:

59842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.010

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

4.9

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-6.2

REVEL

Benign

0.14

Sift

Benign

0.045

Sift4G

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.59

gMVP

0.49

Mutation Taster

=45/55

disease causing

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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PLEKHB2 p.Pro67Leu

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over