Variant 2-68380815-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002664.3(PLEK):c.291G>T(p.Lys97Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,613,520 control chromosomes in the GnomAD database, including 76,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.30 ( 7648 hom., cov: 32)

Exomes 𝑓: 0.29 ( 69337 hom. )

Consequence

PLEK
NM_002664.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.24

Variant links:

Genes affected

PLEK (HGNC:9070): (pleckstrin) Enables phosphatidylinositol-3,4-bisphosphate binding activity; protein homodimerization activity; and protein kinase C binding activity. Involved in several processes, including G protein-coupled receptor signaling pathway; actin cytoskeleton organization; and positive regulation of supramolecular fiber organization. Located in cytoplasm and ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLEK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.30253E-5).

BP6

Variant 2-68380815-G-T is Benign according to our data. Variant chr2-68380815-G-T is described in ClinVar as [Benign]. Clinvar id is 1258238.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEK	NM_002664.3 linkuse as main transcript	c.291G>T	p.Lys97Asn	missense_variant	3/9	ENST00000234313.8
PLEK	XM_047444772.1 linkuse as main transcript	c.291G>T	p.Lys97Asn	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEK	ENST00000234313.8 linkuse as main transcript	c.291G>T	p.Lys97Asn	missense_variant	3/9	1	NM_002664.3	P1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45860

AN:

152000

Hom.:

7653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.394

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.486

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.362

AC:

90821

AN:

251010

Hom.:

19384

AF XY:

0.359

AC XY:

48656

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.295

Gnomad AMR exome

AF:

0.531

Gnomad ASJ exome

AF:

0.339

Gnomad EAS exome

AF:

0.705

Gnomad SAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.291

AC:

425625

AN:

1461404

Hom.:

69337

Cov.:

AF XY:

0.295

AC XY:

214818

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.340

Gnomad4 EAS exome

AF:

0.676

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.319

GnomAD4 genome

AF:

0.302

AC:

45887

AN:

152116

Hom.:

7648

Cov.:

AF XY:

0.308

AC XY:

22944

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.394

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.693

Gnomad4 SAS

AF:

0.486

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.274

Hom.:

14738

Bravo

AF:

0.315

TwinsUK

AF:

0.245

AC:

910

ALSPAC

AF:

0.261

AC:

1005

ESP6500AA

AF:

0.288

AC:

1270

ESP6500EA

AF:

0.257

AC:

2211

ExAC

AF:

0.354

AC:

42937

Asia WGS

AF:

0.539

AC:

1872

AN:

3478

EpiCase

AF:

0.258

EpiControl

AF:

0.257

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.000023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.0000024

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.18

REVEL

Benign

0.14

Sift

Benign

0.48

Sift4G

Benign

0.072

Polyphen

1.0

Vest4

0.23

MutPred

0.56

Loss of MoRF binding (P = 0.04);

MPC

0.36

ClinPred

0.018

GERP RS

4.0

Varity_R

0.28

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over