3-87240719-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014043.4(CHMP2B):c.55C>G(p.Arg19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,468 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHMP2B
NM_014043.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Publications

1 publications found

Variant links:

Genes affected

CHMP2B (HGNC:24537): (charged multivesicular body protein 2B) This gene encodes a component of the heteromeric ESCRT-III complex (Endosomal Sorting Complex Required for Transport III) that functions in the recycling or degradation of cell surface receptors. ESCRT-III functions in the concentration and invagination of ubiquitinated endosomal cargos into intralumenal vesicles. The protein encoded by this gene is found as a monomer in the cytosol or as an oligomer in ESCRT-III complexes on endosomal membranes. It is expressed in neurons of all major regions of the brain. Mutations in this gene result in one form of familial frontotemporal lobar degeneration. [provided by RefSeq, Jul 2008]

CHMP2B Gene-Disease associations (from GenCC):

frontotemporal dementia and/or amyotrophic lateral sclerosis 7
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
amyotrophic lateral sclerosis type 17
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CHMP2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014043.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP2B	NM_014043.4	MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 2 of 6	NP_054762.2
CHMP2B	NM_001410777.1		c.151C>G	p.Arg51Gly	missense	Exon 3 of 7	NP_001397706.1
CHMP2B	NM_001244644.2		c.4-4995C>G		intron	N/A	NP_001231573.1	Q9UQN3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP2B	ENST00000263780.9	TSL:1 MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 2 of 6	ENSP00000263780.4	Q9UQN3-1
CHMP2B	ENST00000472024.3	TSL:5	c.103C>G	p.Arg35Gly	missense	Exon 3 of 7	ENSP00000480032.2	A0A087WW88
CHMP2B	ENST00000676705.1		c.103C>G	p.Arg35Gly	missense	Exon 3 of 7	ENSP00000504098.1	A0A087WW88

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251142

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000137

AC:

AN:

1460468

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726672

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110844

Other (OTH)

AF:

0.00

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.85

Eigen

Benign

0.13

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.096

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.33

MutationAssessor

Pathogenic

3.5

PhyloP100

1.5

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.51

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

0.22

Vest4

0.77

MutPred

0.62

Loss of MoRF binding (P = 0.0052)

MVP

0.83

MPC

0.27

ClinPred

0.86

GERP RS

3.6

Varity_R

0.76

gMVP

0.41

Mutation Taster

=50/50

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over