Variant chr2-68388414-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002664.3(PLEK):c.685A>C(p.Asn229His) variant causes a missense change. The variant allele was found at a frequency of 0.00859 in 1,609,922 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0087 ( 88 hom. )

Consequence

PLEK
NM_002664.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.18

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007189125).

BP6

Variant 2-68388414-A-C is Benign according to our data. Variant chr2-68388414-A-C is described in ClinVar as [Benign]. Clinvar id is 769563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEK	NM_002664.3 linkuse as main transcript	c.685A>C	p.Asn229His	missense_variant	6/9	ENST00000234313.8
PLEK	XM_047444772.1 linkuse as main transcript	c.657+1728A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEK	ENST00000234313.8 linkuse as main transcript	c.685A>C	p.Asn229His	missense_variant	6/9	1	NM_002664.3	P1
PLEK	ENST00000474788.1 linkuse as main transcript	n.473A>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.00754

AC:

1147

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000966

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0234

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00802

AC:

2016

AN:

251284

Hom.:

AF XY:

0.00799

AC XY:

1085

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00486

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.0236

Gnomad NFE exome

AF:

0.0113

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00870

AC:

12685

AN:

1457662

Hom.:

Cov.:

AF XY:

0.00865

AC XY:

6275

AN XY:

725402

show subpopulations

Gnomad4 AFR exome

AF:

0.000988

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00456

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00275

Gnomad4 FIN exome

AF:

0.0241

Gnomad4 NFE exome

AF:

0.00949

Gnomad4 OTH exome

AF:

0.00707

GnomAD4 genome

AF:

0.00753

AC:

1147

AN:

152260

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

586

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.0234

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00832

Hom.:

Bravo

AF:

0.00543

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.00839

AC:

1019

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00907

EpiControl

AF:

0.00796

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.18

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Benign

0.068

Sift

Benign

0.53

Sift4G

Benign

0.54

Polyphen

0.58

Vest4

0.57

MVP

0.61

MPC

0.20

ClinPred

0.021

GERP RS

5.2

Varity_R

0.16

gMVP

0.090

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