2-68395703-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002664.3(PLEK):ā€‹c.940C>Gā€‹(p.Leu314Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,614,030 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 Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00020 ( 0 hom., cov: 31)
Exomes š‘“: 0.000026 ( 0 hom. )

Consequence

PLEK
NM_002664.3 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23192862).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLEKNM_002664.3 linkuse as main transcriptc.940C>G p.Leu314Val missense_variant 9/9 ENST00000234313.8
PLEKXM_047444772.1 linkuse as main transcriptc.835C>G p.Leu279Val missense_variant 8/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLEKENST00000234313.8 linkuse as main transcriptc.940C>G p.Leu314Val missense_variant 9/91 NM_002664.3 P1
PLEKENST00000474788.1 linkuse as main transcriptn.728C>G non_coding_transcript_exon_variant 4/42

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152082
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000520
AC:
13
AN:
249966
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135210
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.0000260
AC:
38
AN:
1461830
Hom.:
0
Cov.:
32
AF XY:
0.0000193
AC XY:
14
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00102
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000204
AC:
31
AN:
152200
Hom.:
0
Cov.:
31
AF XY:
0.000202
AC XY:
15
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.000746
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000181
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 19, 2023The c.940C>G (p.L314V) alteration is located in exon 9 (coding exon 9) of the PLEK gene. This alteration results from a C to G substitution at nucleotide position 940, causing the leucine (L) at amino acid position 314 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.33
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.8
N
REVEL
Uncertain
0.45
Sift
Benign
0.10
T
Sift4G
Uncertain
0.023
D
Polyphen
0.91
P
Vest4
0.47
MVP
0.83
MPC
0.29
ClinPred
0.14
T
GERP RS
4.8
Varity_R
0.82
gMVP
0.29

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.

Other links and lift over

dbSNP: rs150306558; hg19: chr2-68622835; API