GeneBe

NM_020631.6:c.2160_2168dupGGAGGAGGA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_020631.6(PLEKHG5):​c.2160_2168dupGGAGGAGGA​(p.Glu721_Glu723dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,445,120 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PLEKHG5
NM_020631.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.980

Publications

13 publications found
Variant links:
Genes affected
PLEKHG5 (HGNC:29105): (pleckstrin homology and RhoGEF domain containing G5) This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]
PLEKHG5 Gene-Disease associations (from GenCC):
  • neuromuscular disease
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • Charcot-Marie-Tooth disease recessive intermediate C
    Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • neuronopathy, distal hereditary motor, autosomal recessive 4
    Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_020631.6

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLEKHG5NM_020631.6 linkc.2160_2168dupGGAGGAGGA p.Glu721_Glu723dup disruptive_inframe_insertion Exon 19 of 21 ENST00000377728.8 NP_065682.2 O94827-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLEKHG5ENST00000377728.8 linkc.2160_2168dupGGAGGAGGA p.Glu721_Glu723dup disruptive_inframe_insertion Exon 19 of 21 2 NM_020631.6 ENSP00000366957.3 O94827-5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000623
AC:
9
AN:
1445120
Hom.:
0
Cov.:
33
AF XY:
0.00000556
AC XY:
4
AN XY:
719222
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32410
American (AMR)
AF:
0.00
AC:
0
AN:
44520
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25980
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39620
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85662
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51962
Middle Eastern (MID)
AF:
0.000525
AC:
3
AN:
5712
European-Non Finnish (NFE)
AF:
0.00000364
AC:
4
AN:
1099476
Other (OTH)
AF:
0.00
AC:
0
AN:
59778
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.419
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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.:
31
Alfa
AF:
0.0000399
Hom.:
19
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.98
Mutation Taster
=84/16
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs113541584; hg19: chr1-6529182; API