Variant 1-6469122-TTCCTCCTCCTCCTCCTCC-TTCCTCCTCCTCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_020631.6(PLEKHG5):c.2163_2168delGGAGGA(p.Glu722_Glu723del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00862 in 1,588,674 control chromosomes in the GnomAD database, including 99 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E721DEQEEEEEEEEEE) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.014 ( 35 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 64 hom. )

Consequence

PLEKHG5
NM_020631.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.94

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 links:

PLEKHG5 (HGNC:):

PLEKHG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-6469122-TTCCTCC-T is Benign according to our data. Variant chr1-6469122-TTCCTCC-T is described in ClinVar as [Benign]. Clinvar id is 194977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-6469122-TTCCTCC-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2041/145478) while in subpopulation AFR AF= 0.0316 (1126/35584). AF 95% confidence interval is 0.0301. There are 35 homozygotes in gnomad4. There are 1017 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHG5	NM_020631.6 linkuse as main transcript	c.2163_2168delGGAGGA	p.Glu722_Glu723del	disruptive_inframe_deletion	19/21	ENST00000377728.8	NP_065682.2	O94827-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHG5	ENST00000377728.8 linkuse as main transcript	c.2163_2168delGGAGGA	p.Glu722_Glu723del	disruptive_inframe_deletion	19/21	2	NM_020631.6	ENSP00000366957.3		O94827-5

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2037

AN:

145374

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00915

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00927

Gnomad SAS

AF:

0.00956

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00813

Gnomad OTH

AF:

0.0114

GnomAD3 exomes

AF:

0.0115

AC:

2258

AN:

196576

Hom.:

AF XY:

0.0110

AC XY:

1178

AN XY:

106916

show subpopulations

Gnomad AFR exome

AF:

0.0349

Gnomad AMR exome

AF:

0.00903

Gnomad ASJ exome

AF:

0.00711

Gnomad EAS exome

AF:

0.0107

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.00906

Gnomad NFE exome

AF:

0.00986

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.00808

AC:

11658

AN:

1443196

Hom.:

AF XY:

0.00801

AC XY:

5753

AN XY:

718176

show subpopulations

Gnomad4 AFR exome

AF:

0.0287

Gnomad4 AMR exome

AF:

0.00726

Gnomad4 ASJ exome

AF:

0.00490

Gnomad4 EAS exome

AF:

0.00573

Gnomad4 SAS exome

AF:

0.00796

Gnomad4 FIN exome

AF:

0.00766

Gnomad4 NFE exome

AF:

0.00757

Gnomad4 OTH exome

AF:

0.0101

GnomAD4 genome

AF:

0.0140

AC:

2041

AN:

145478

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1017

AN XY:

71126

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00913

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00910

Gnomad4 SAS

AF:

0.00916

Gnomad4 FIN

AF:

0.00867

Gnomad4 NFE

AF:

0.00814

Gnomad4 OTH

AF:

0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 31, 2015

- -

Neuronopathy, distal hereditary motor, autosomal recessive 4;C3809309:Charcot-Marie-Tooth disease recessive intermediate C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

PLEKHG5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 04, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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